Talk:Coeliac disease/Archive 3

Refractory Disease
Refractory disease
 * A tiny minority of patients suffer from refractory disease, which means they do not improve on a gluten-free diet. This may be because the disease has been present for so long that the intestines are no longer able to heal on diet alone, or because the patient is not adhering to the diet, or because the patient is consuming foods that are inadvertently contaminated with gluten. If alternative causes have been eliminated, steroids or immunosuppressants (such as azathioprine) may be considered in this scenario.[6]

The above paragraph maybe considered misleading and opinionated. Refractory Celiac Disease can be broken down into groups RCD1 and RCD2. RCD1 is found in people who are DQ2 heterozygotes or DQ8 and are found in general is disease diagnosed over the age of 35. RCD2 is found in people who are DQ2/DQ2 (70%) and really has little to do with 'cheating on wheat' it is found in older onset cases. RCD2 generally appears with 3 years of diagnosis in patients generally over the age of 45, and is associated with precancerous tissues, it is generally untreatable with drugs (except bone marrow replacement and chemotherapy) and generally progresses to EATL. In many cases, at the time of diagnosis the precancerous tissue is already present. RCD2 is generally fatal within 5 years. Nor is it a condition of failure to heal, specifically, as a result of prolonged disease, but the constant stimulation by T-cells that are no longer require antigen, gliadin. If those cells are oblated the GI tract should heal. In RCD I there are markers that indicated some sort of cellular transformation, in RCD II there are typically clonal lymphocyte cell lines present and ussually spreading.

In addition recent studies show that DQ2.5/DQ2 individuals have more serious histological pathology and this corroborates with the finding of RCD2 (although the RCD2 study did not do SSP-PCR genotyping). The enhanced stimulation of homozygotes and the duration of the disease are likely major factors in whether T-cells will undergo transformation. Pdeitiker 04:04, 28 September 2007 (UTC)


 * This is based on the AGA position document. Go complain to them. Obviously compliance is a major issue. JFW | T@lk  15:03, 8 October 2007 (UTC)


 * Not complaining, I was made aware of a specific case in which a persons doctor continued to insist that the patient was cheating as her symptoms aggressively returned, she went about contacting and threatening food and drug companies. Despite the fact she had CD+ 6 children (i.e. very plausible DQ2 homozygote), after switching to a physician that was familiar with RCD, she is now being treated for RCD. RCD2 is an aggressive and life threatening disease and may flare up within 3 years on a gluten free diet, largely late onset in origin but in some cases can be earlier in onset, and has a very strong genetic component. user:pdeitiker) 18:38, 18 December 2007

Messing around with gliadin
Gianfrani et al report T-cell reactions, specifically affinity to DQ2, to gluten transamidated with an amine donor. ... JFW | T@lk  15:15, 8 October 2007 (UTC)

More CD over time
The Finnish coeliac lot seem to think that a higher diagnostic level of suspicion does not explain the rise in incidence over time: JFW |  T@lk  11:36, 19 October 2007 (UTC)

Review
In this week's NEJM. May be interesting, for those with access :) Fvasconcellos (t·c) 22:42, 24 October 2007 (UTC)

Pathophysiology
I think the section for Pathophysiology needs to be reviewed since it makes too much mention to genetics specifically, perhaps a more clear, consise explanation should be given instead of genetics only. PLEASE!!! it's rather confusing!!!Chaotic rach 23:41, 4 November 2007 (UTC)


 * Genetics is a major issue in coeliac disease, and needs substantial coverage. What information do you think is presently lacking? JFW | T@lk

Liver
Review on liver in coeliac disease: JFW |  T@lk  23:32, 5 November 2007 (UTC)


 * - all about oral lesions. Many coeliacs have dental enamel problems and soft tissue lesions. JFW | T@lk  17:48, 25 November 2007 (UTC)

Indo-European
Where does the van Heel article say anything about Indo-Europeans. The data suggests that North-Americans and Europeans have a similar epidemiology (1%). The prevalence seems to be lower among non-Caucasians. Do you have a study about Iraninans or North-Indians?

See http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16564784&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

and also

http://www.consensus.nih.gov/2004/2004CeliacDisease118html.htm

They both mention studies in North America and Europe being similar. Whence the generalization to Indo-European (which, approrpriately or not, the present zeitgeist has relegated to Linguistics) 138.5.88.219 (talk) 02:35, 13 December 2007 (UTC)smorr


 * For genetic risk factors here are the frequencies of DQ2.5 and HLA-DQ8. DQ2.2 is higher in Iberia to central Asia. Reports coming from India some slight differences in genetic risk. DQ2.5 is not abundant in India, and associations with DQ2 are not as clear as in NW Europe. North American disease frequencies are comparable to British disease frequencies within the Caucasian population. The gene frequencies of DQ2 and DQ8 are comparable. Some areas of Europe have relatively low frequencies of disease, and parts of India have almost no genetic susceptibility.


 * In terms of disease genes here are the gene frequencies from north India Pdeitiker (talk) 05:09, 25 December 2007 (UTC)


 * The geographical distribution of gene frequencies still wouldn't justify using Indo-European in this context in my personal opinion. Indo-European is a linguistic term, and as far as I can see, Wikipedia's own disambiguation page only lists linguistic definitions, although it does talk about 'Indo-European people'. Put it this way, is there anything to show that the gene frequency was not already present before the Indo-European language expansion?  Maybe some other term should be used, or just a simple description of European, Central Asian and North Indian populations, if a geographical description is needed. Stevebritgimp (talk) 13:20, 18 May 2008 (UTC)
 * Or put another way while I think about it: 1) If this were so, Coeliac disease would be a strong indicator of the genetic unity of a very widespread linguistic group - itself probably news to historians and linguists. 2) If this is unproven it would be conclusion drawing, and basically contrary to WP:SYNTH (I think) - a synthesis would be made of geographical distribution and linguistic characteristics - that would need to be attested in a Reliable Source (hell, now I'm sounding like a WP rules lawyer - definitely not me!). Cheers.  Stevebritgimp (talk) 13:24, 18 May 2008 (UTC)

Celiac Disease, T1D, RA linked to 4q27
Novel Association in Chromosome 4q27 Region with Rheumatoid Arthritis and Confirmation of Type 1 Diabetes Point to a General Risk Locus for Autoimmune Diseases. Zhernakova et al.


 * Recently, association of celiac disease with common single-nucleotide polymorphism (SNP) variants in an extensive linkage-disequilibrium block of 480 kb containing the KIAA1109, Tenr, IL2, and IL21 genes has been demonstrated in three independent populations (rs6822844 ). The KIAA1109/Tenr/IL2/IL21 block P p 1.3#10514 corresponds to the combined Idd3 locus in the nonobese diabetic mouse model of type 1 diabetes (T1D). This block was recently found to be associated with T1D in a genomewide association study, although this finding lacks unequivocal confirmation.We therefore aimed to investigate whether the KIAA1109/Tenr/IL2/IL21 region is involved in susceptibility to multiple autoimmune diseases. We tested SNP rs6822844 for association with disease in 350 T1D-affected and 1,047 rheumatoid arthritis (RA)–affected Dutch patients and in 929 controls. We replicated the association with T1D (P p .0006; OR 0.64 [95% CI 0.50–0.83]), and revealed a similar novel association with RA (P p .0002; OR 0.72 [95% CI 0.61–0.86]). Our results replicate and extend the association found in the KIAA1109/Tenr/IL2/IL21 gene region with autoimmune diseases, implying that this locus is a general risk factor for multiple autoimmune diseases.[End Abstract]

User:Pdeitiker 18:31, 18 December 2007 (UTC)

Cardiovascular disease
In contrast to the Cambridge study cited in Van Heel/West, there is now some linkage with cardiovascular disease JFW |  T@lk  09:06, 23 December 2007 (UTC)


 * good, its about time. The misconception of many physicians is that celiacs are underweight and are starving to death. Many celiacs have weight problems that can be attributed to partial maladsorption. I lost 25 lbs after going on a GF diet, largely because of increased adsorption of omega-3 fats and vitamin B. Celiacs can also be at risk because of secondary conditions such a rheumatoid arthritis or other debilitating conditions that result in lowered mobility. Other problems includes increased reliance on carbs as a result of protein/saturated fat intolerance and pancreatic insufficiency. This then sets up a condition if the person is not aware of the affects of fast carbs (starch) on saturated fat catabolism and cholesterol production, increased triglycerides and low density lipoprotein concentrations.Pdeitiker (talk) 04:59, 25 December 2007 (UTC)

Phil, are you certain you want to share personal experience with us? How certain are you about omega-3 and vitamin B absorption after starting a gluten-free diet? Did you get them checked? JFW | T@lk  07:49, 6 January 2008 (UTC)


 * One is never sure about sharing personal experiences, lol. There is chronic fatique and depression association with celiac disease. Some of this is attributed to the maladsoption of essential fatty acids. In addition sources of foods that are rich in certain vitamins tend also to be rich in protein, which can be the source of secondary allergic conditions (eggs, fish, etc). Gluten-sensitive_enteropathy_associated_conditions links. Several CD specific conditions, such as localized epileptic seizures are attributed to folic acid deficiency that a recent paper (I will have to look up) claims is a secondary consequence of vitamine B12 decline, increasing B12 results in a rise of folic acid without additional folic acid treatment. Why B12 falls off in celiac disease is unclear, but omega-3s, B6, B12 and secondarily folic Acid all appear to have linked behavior. Not to give details but I do have a folic-deficiency related condition. These alone can explain at least some of the chronic fatique association. I should note however, starting last summer I moved away from processed grains to a complete whole grains-starch source diet, since then I have no general need for vit b supplimentation, but still maintain relative high O-3 intake.  Many celiacs I have corresponded with complain of an addiction 'cravings' to fast carbs, I certainly can concur with this state given that 4 years ago I could eat very little protein because of the allergic responses, the body develops cravings for these things and these remain on a gluten free diet (at least for the year one is sorting out allergies). I still have difficulty maintaining certain species, e.g. cholesterol runs well below normal which means that HDL is usually a high percentage of TSC. Not sure why this is.


 * Given that late onset disease diagnosis is on the rise, I think the medical community has to face at least the fact: If the disease rate is not increasing then symptomatic disease is on the rise. Since my area of specialization is autoimmune disease it is relatively clear and certain that autoimmune diseases are rising in frequency and westernization of diet (increased saturated fats, increased processed foods, increased fast carbohydrates, affluence). The case for HLA-DQ and diet appears to be strengthening and does not appear to be restricted to DQ2 and DQ8. Part of the current 'Health Crisis' of the west is the genetic incompatibility of subpopulations within European derived peoples, or near entire groups incompatibility with the common western diet. The genetic factors within this overlap with HLA mediated and other immunological diseases. Or to put it more simply, some of us should be very carefully selected what we eat of a western diet. A recent paper by John Hawks and company (PNAS) shows that a large percentage of variable sites in the human genome have undergone _regional_ selection in the last 5000 years, a previous paper showed that a high percentage of these genes are in the immunological and digestion/metabolism area. So that my unabashed personal experiences reflect something that is becoming more widely established in the anthropology circles, we are not all alike.


 * Therefore it is not surprising that we are seeing a flip between very severe late onset cases that are starving, in which factors triggering symptomacy may have been enteric infections (rotavirus, enterovirus, influenza virus) are also associated with weight loss - situations that may have been identified back in the early half of the 20th century . . . .but now a class of symptomatic patients is emerging where the damaging agents might be an excess of certain chemicals in the diet which include spikes in glucose as a result of starch metabolism. Other factors include aspirin, NSAIDS, MSG, sodium benzoate, that damage or weaken the lining of the GI tract, things people consume more of relative to 50 years ago. Instead of seeing these patients in a emaciated moribund state they are being identified in the clinics much earlier.Pdeitiker (talk) 15:32, 2 February 2008 (UTC)


 * No sooner said. Arch Pediatr Adolesc Med. 2008 Feb;162(2):164-8. Emerging new clinical patterns in the presentation of celiac disease. Telega G, Bennet TR, Werlin S.


 * "...The number of patients diagnosed with celiac disease increased from 1 in 1986 to 93 in 2003. The mean age at diagnosis increased from 5.32 years for patients diagnosed before 1995 to 8.70 years for patients diagnosed after 1995. Gastrointestinal symptoms dominated in children younger than 3 years, whereas in children older than 3 years, the majority presented with non-gastrointestinal indications. The percentage of patients presenting with gastrointestinal symptoms alone decreased during the study period; 11.2% of patients diagnosed with celiac disease were overweight (body mass index > 90). CONCLUSIONS: Our study provides a unique longitudinal follow-up of clinical practice over a 17-year period. Currently, patients with celiac disease usually do not present with classic symptoms; they are more likely to be asymptomatic school-aged children who belong to a high-risk group...."Pdeitiker (talk) 00:50, 16 February 2008 (UTC)

Males in DQ2/DQ8 negativity
finds (in a smallish series) that CD is more common in women, that there is an usually high rate of DQ2/8 negativity in the male group, and that transmission of DQ2/DQ8 genotype from fathers to daughters posed a relatively high risk. Imprinting? JFW | T@lk  07:49, 6 January 2008 (UTC)

Here we go again...
- if tTG antibody is >30 units/mL (10 the upper limit of normal) - which is the case in 50% of the cases - duodenal biopsy may be unnecessary because of the very high sensitivity and specificity of the test at this level. JFW | T@lk  21:25, 13 January 2008 (UTC)


 * Why 'here we go again', I would think this is common sense. I am waiting for the paper to come out that looks at tTG deposits and concludes that peroral biopsy as a stand alone diagnostic measure is obsolete and inaccurate.Pdeitiker (talk) 17:20, 3 February 2008 (UTC)

I wrote "here we go again", because guidelines presently demand a duodenal biopsy at least once in the disease course, and it is my personal opinion that neglecting to do so will lead to important comorbidities being missed, such as giardiasis or Whipple's. JFW | T@lk  09:43, 24 February 2008 (UTC)


 * hmmmm, what do you do about docs that, in the new health care restricted system, do not want to do biopsy. I would have loved to have had a biopsy, when I told my assigned PCP I thought I had CD he told me it was a fatal disease of small children and laughed. The first time I got to see a GI phys was for GERD 3 years after the fact. I work in a medical school. I was extremely fortunate that I know how to do DNA and Antibody work. I was trying to save my job and stay alive, I couldn't wait until MDs figured it was time to do the right thing.
 * I picked up someone in my screening work that was a suspicious of CD because of genetic and other known CD risk factors, in September this individual ask GI physician (after having gone through a GI crisis, treated for anti-biotics, including one specifically designed to treat GI yeast infections) for an ATA-IgA/IgG test and it was not given. After a query about what I thought it was and how it was treated I gave her some papers and against my recommendation, this individual went on the GF diet and saw immediate improvement. It will be lucky at this point if the individual gets the ATA test done and interpretation may be compromised. If I have my numbers correct the individual has been to see the PCP or GI about 7 times since September for the same issues. You tell us what to do, the individual works in a medical environment and still has no ability to convince the health care system to establish a probability-recommended course of action. Is there a button that the patient can push that gets MDs to start acting like scientist, start reading papers when patients present relevant information??? Nare judge a man 'till you walk 5 miles in his shoes. Pdeitiker (talk) 14:41, 20 March 2008 (UTC)

Wheat allergy vs gluten intolerance
This article does not distinguish between the two concepts, which although related, are not the same.  Socrates2008 ( Talk )   23:45, 1 February 2008 (UTC)


 * See Wheat allergies page. You can find the criteria for 3 wheat related diseases on Gluten sensitivity
 * Comparative pathophysiology of Gluten Sensitivities.


 * Gluten Sensitive Enteropathy (Major:Coeliac disease) is a subset of gluten sensitivities. It is defined by a number of phenomena in addition to allergic responses: Defined T-helper cell response, anti-Host-autoantibody presence, distinct pathology. One recent paper claims that CD in its advanced phases suppresses allergic responses even to gluten, and it has been observed that many chronic late onset cases lack anti-gliadin antibodies. It is therefore possible to have gluten allergy and not have celiac disease, and to have coeliac disease and not have anti-gliadin antibodies or gluten allergy (Noting that these studies have yet to stand of to the scrutiny of wheat hydrolysate testing). Pdeitiker (talk) 14:45, 2 February 2008 (UTC)


 * You sound like specialist in this area - would you mind updating the article to clarify? i.e. expand the intro to explain where this article on Coelic disease fits into the wider background of gluten-related sensitivities.  Socrates2008 ( Talk )   21:21, 2 February 2008 (UTC)


 * The complaint is that the GS article needs some 'de jargonization' but at the moment I am not sure how. What is considered jargon here is the 'lingua franca' elsewhere.Pdeitiker (talk) 03:19, 3 February 2008 (UTC)


 * I agree that a clear distinction needs to be made, and I have added this in the intro. I don't think any space should be devoted to the differences in pathophysiology, because that is something the wheat allergy page (presently a stupid laundry list) should do.


 * I don't know if I would call it a 'stupid laundry list', I agree, there is clearly enough information on this page, and until either gluten allergy or idiopathic gluten-sensitive neuropathy can be linked more specifically to GSE they should not be discussed here. However the differences in Pathophysiology need to be on the Gluten sensitivity page, if you place them on the allergy page you have the same conflict as placing them on the Coeliac disease page. PD (talk)


 * I see the problem, two pages, will merge the two articles under wiki-consistent name. BTW, when are you going to fix that table that has two rows with the same labels? PD (talk)


 * I have created a temporary page that I intend to replace the 'stupid laundry list' page others have stubbed for Wheat allergy.Proposed replacement of wheat allergy If this is acceptable I will replace the current page and redirect Wheat allergies to wheat allergy. From a naming convention point of view I would argue that there is no single wheat allergen but that allergic responses to different proteins can affect different systems, so it might be correct to call them wheat allergies instead of wheat allergy. Any thoughts? Pdeitiker (talk) 05:20, 11 February 2008 (UTC)
 * You should be having this discussion on the talk:Wheat allergy page, not here. Also, wheat allergy and wheat allergies need to be merged.   Socrates2008 ( Talk )   07:31, 11 February 2008 (UTC)


 * Pdeitiker, you are the principal author of a whole raft of articles (gluten sensitivity, gluten-sensitive enteropathy associated conditions, gluten-sensitive idiopathic neuropathies) that are chock-a-block with jargon that I have not encountered anywhere else in the literature. I have so far resisted having them merged or cleaned up, but I really wish you could try to improve the readability of your handiwork. JFW | T@lk  12:31, 10 February 2008 (UTC)


 * That is the reason I did not want to do them at all. I was asked by a few lay people because they get results from their MDs and they do not know whether they have allergy or intolerance or how the two can differ, and then finally, and most heinous, a certain third-party testing lab who uses this 'jargonistic' information about very rare idiopathic disorders to convince those that are tested that they have a gluten sensitivity. So prevalent was this diagnostics and belief that something needed to be done. The wheat allergy page is justified, but the 'idiopathic gluten sensitivity' falls into what I consider to be on the level of '..Spears current events'. . . ..


 * This is fairly important issue and I welcome critiques. However should we really discuss this on this page?
 * There are several issues on those pages that after having new literature and reread old literature I want to change. For example, on the wheat allergy page all psuedoallergies group and redirected off page. When the page was written there was not a page on anti-yeast allergies. However, I would like to go over all the literature at a sitting to see how it best be represented. At the time the page was written the issue of Atopia and wheat sensitive exercise induced anaphylaxis was not properly discussed on either the Atopia or the EIA page and there was a battle between authors of the Urticaria and EIA page going on, if you link to a page where the explanation is equally bad . . . . . You will noticed I changed the name of the page, even though gluten allergy is specifically mentioned in several papers, it is becoming evident that allergies cannot and should not be defined in the same way gluten intolerance is defined.PD (talk)

Monosodium glutamate/Glutamic acid
Are there any issues for people with gluten sensitivity to monosodium glutamate and glutamic acid (both of these are highly processed forms of gluten)? Either way, might be worth a mention.  Socrates2008 ( Talk )   12:20, 10 February 2008 (UTC)


 * I don't know. Is that your personal theory? MSG and glutamic acid are amino acids, and it is unusual to have immune-mediated reactions against amino acids. The only possibility would be contamination with gliadin peptides. How about you Google it and let us know? JFW | T@lk  12:35, 10 February 2008 (UTC)


 * No, I don't have a theory. However have read about hidden gluten as an additive in some foods such as ice-cream, so was wondering if these were an issue too.   Socrates2008 ( Talk )   13:12, 10 February 2008 (UTC)

As a non-scientist, non-physician member of the celiac community for over twenty-five years I would like to interject a simple answer to this question: 1)Beware of anecdotal "information" bandied about by fellow celiac sufferers. Too often it is not supported by fact. 2) Certain substances (e.g. Monosodium Glutamate) are simply irritating to the unhealed tissues of a recently diagnosed celiac. These items are best avoided in the diets of children anyway and in both children and adults may be introduced in small quantities later. Remember just because you have a hammer, everything isn't a nail.


 * There have been inferences made about Aspirin, MSG, Sodium benzoate, FD&C yellow, NSAIDS. I believe based upon what I have read that microperforations of the GI tract may have more to do with allergies and inflamatory bowel illnesses than Coeliac disease, specifically. Aspirin and Exercise have both been implicated in Uticaria and Exercise Induced Anaphylaxis and it has been reported that in the case of EIA that these agents allow gliadin peptides to enter the blood stream from the GI tract. The modality of glutamate and benzoate action is not clear. Allergic disorders can aggrevate autoimmunity, as appears to be the case with rheumatoid arthritis, and entering of digested peptides into the blood may be a factor in several disorders. With regard to Coeliac disease these may be involved in triggering disease, but once disease is triggered it seems unlikely they play a maintenance role and the damage induced is relatively minor compared to other agents. PD

Peptides in the bloodstream? That is a highly controversial theory. JFW | T@lk  09:39, 24 February 2008 (UTC)

Haptoglobin variants, Maladsorption and CD
Clin Chem. 2008 Feb 7. Haptoglobin Polymorphism: A Novel Genetic Risk Factor for Celiac Disease Development and Its Clinical Manifestations. " . . .RESULTS: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20-1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60-3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. . . . "

Not sure what to make of thisPdeitiker (talk) 00:23, 16 February 2008 (UTC)


 * Perhaps this needs to await further studies. What role does haptoglobin have in immunomodulation? JFW | T@lk  09:39, 24 February 2008 (UTC)

Gluten-free diet is protective against subsequent (secondary) autoimmune diseases
Clin Gastroenterol Hepatol. 2008 Feb 5 Incidence of Autoimmune Diseases in Celiac Disease: Protective Effect of the Gluten-Free Diet.

"... The cumulative risk of subsequent autoimmune disease was lower in patients compliant to a gluten-free diet versus noncompliant patients (at 10 years, 6% +/- 2% vs 15.6% +/- 5.9%, respectively; P = .02). The incidence of autoimmune diseases was 5.4 per 1000 patient-years during adherence to a gluten-free diet versus 11.3 per 1000 patient-years during nonadherence to the diet (P = .002). Results were similar in both the pediatric and the adult populations. CONCLUSIONS: Celiac patients most at risk for autoimmune disease are those diagnosed early in life and having a family history of autoimmunity. The gluten-free diet has a protective effect."

This is one of my pet 'harps' that the importance of secondary diseases, many of them rare in celiacs, are increased for celiac disease. The statistics of the problem is one that I deal with, there are many rare diseases that are at ever so slightly increased risk in celiac disease, many of these are autoimmune diseases that are 'discounted' in association. While risk of individual disease is rare the number or these rare diseases that are associated is high, therefore overall the risk of celiacs acquiring a secondary disease is high, it is simply impossible to predict which one. Celiacs often contain a second allele (either DRB1 or DQB1) that can increase the risk of the secondary disease.

According to this study going on a gluten-free diet decreases the risk to almost 1/3rd which for many disease is approximately normal risk. While it may appear that GF diet solves the problem, other factors, allergens in particular, may elevate risk for diseases like thrombosis or arthritis and therefore simply excluding gluten is not the solution to the problem of autoimmune disease triggered by inflammatory disease.Pdeitiker (talk) 00:36, 16 February 2008 (UTC)


 * That sounds controversial and not ready for prime time. JFW | T@lk  09:39, 24 February 2008 (UTC)

BBC news article
added an external link to a BBC article about a patient with coeliac disease. I generally find that external links to news resources are a bad idea. If the topic of the news article is relevant, this should be integrated with the article and footnoted to the news article.

In this particular instance, the article is about a patient with coeliac disease. Much of his disease course is typical (diagnosis was on the basis of atypical symptoms) and he needs characteristic treatment with a diet. The article has several inaccuracies that make it less suitable still: it suggests that colon cancer risk is raised in untreated CD (small bowel lymphoma and carcinoma was undoubtedly intended, but these are different diseases), red blood cells are not "malformed" in B12 deficiency (they are enlarged and have hypersegmented nuclei) and B12 is not absorbed in the upper part of the gut (it is absorbed in the terminal ileum), gluten might be present in oats but oats are not necessarily a problem in coeliac disease... The concern about his 4-year old daughter could be alleviated if she was tested for HLA-DQ2 and coeliac serology. JFW | T@lk  12:55, 24 February 2008 (UTC)

Comment: I added the link because:
 * The Wiki article is currently presented from a medical point of view - the link adds the missing patient perspective.
 * I could not see any easy way to integrate the story in the current article without upsetting someone (although I seem to have succeeded on that score anyway)
 * The linked article is from a reliable source, the BBC - an organisation that is cited widely by Wikipedia.
 * The linked article fits under the guidelines of What should be linked - i.e. "Sites with other meaningful, relevant content that is not suitable for inclusion in an article, such as reviews and interviews."
 * The linked article covers the correct subject matter, Coeliac disease
 * The linked article is easy for lay readers to read and understand.
 * The linked article includes information that is not present in this article, e.g. problems faced trying to follow a gluten-free diet for the first time.

Lastly, the reasons given by Jfdwolff for removing this link amount to WP:OR. I note too that my edit has been reverted for a second time BEFORE consensus has been reached here. (Kindly refrain from reverting again until this issue is settled here.) I shall be happy to accept the consensus of other editors about the inclusion or exclusion of this link - so please indicate your preference below. Thank you.  Socrates2008 ( Talk )   09:31, 25 February 2008 (UTC)


 * A problem with "the patient perspective" is that everyone is different. There simply isn't room to discuss (or link to) all the different ways coeliac disease may affect someone's life. The patient charity web sites are better at this, and may include personal stories. These are already linked-to by this article. I'd also trust those websites to check their facts better than some journalist. The story shouldn't be integrated as the person involved is utterly non-notable. The BBC is a reliable source for news, not medical facts. JFW has indicated the article's shortcomings in this regard. Much of the article reports what the interviewee said about his medical story, and it appears the journalist hasn't checked to see if this was imprecise/incorrect, or whether she has misunderstood what she was told.
 * See BOLD, revert, discuss cycle for why JFW's revert was acceptable practise and your revert of his revert was not. -- Colin°Talk 14:00, 25 February 2008 (UTC)
 * Colin, thanks for the feedback. I wouldn't exactly call my edit bold.  On the contrary, it was a single external link that didn't change anything in the substance of the article.   Socrates2008 ( Talk )   14:17, 25 February 2008 (UTC)
 * You're right, but that's the name of the essay (it isn't even a guideline). See External links for more guidance (though I suspect you already have). I think you made a good-faith addition, but on balance we already have plenty patient-friendly links for sites that are far more comprehensive than one short news story. If everyone added a useful/interesting link, the article would be nothing but links. So JFW's edit was mainly to keep to a sensible number of really good links. For example, if this disease was extremely rare, then the BBC interview might well be useful, due to the paucity of coverage by any media. Colin°Talk 14:27, 25 February 2008 (UTC)

Socrates2008 - I sometimes remove links without reviewing them closely, but in this case I gave the BBC article a close look before I removed it on the grounds mentioned above. Do you disagree that the interview is full of errors?

I disagree that every medical article needs something from "the patient's perspective". A good medical article discusses this as part of its content, and if you feel this is lacking from this article then please make content changes to that effect. The article already states that the diet can be cumbersome and that quality of life may be decreased even while on GFD. Is that not sufficiently aimed at the patient's perspective? JFW | T@lk  20:41, 25 February 2008 (UTC)

Patient perspectives
With regard to coeliac disease and the very high late onset misdiagnosis rate, one could argue the late onset disease is an assortment of patient perspectives. Since some people enter the process with a secondary autoimmune condition the quality of life may decrease on GFD, but if they do not abstain, quality of life may decrease with the next secondary condition. And, with regard to that RCD2 and EATL can markedly decrease the quality of a markedly shortened life. There are very few instances of late onset disease where the symptoms between patients match exactly, there are a few that are frequent such as abdominal inflammation, chronic fatique, "brain fog". Even with these the path to diagnosis may begin with autoimmune thyroiditis, dermatitis herpetiformis, or some other condition.

One of the problems with Coeliac disease page is that it focuses on the most common symptoms but if fails to detail higher frequency than normal symptoms and conditions seen in celiac disease. When all these are combined they are more common than the most common preclinical symptoms. These collections of symptoms are the patients perspective and clinical ignorance of these lessor symptoms is a major reason for the high misdiagnosis rate and is also part of the patient perspective on the process. Pdeitiker (talk) 12:42, 12 March 2008 (UTC)


 * With respect, I think you are completely wrong. The article makes it abundantly clear that presentation may be subtle and relating to nonspecific symptoms. It also cites recent UK guidance about screening for coeliac disease in typical "dustbin syndromes" where one would find many cases of CD, such as IBS and chronic fatigue.
 * Do you have a reliable source that sensibly enumerates the "higher frequency of symptoms and conditions"? JFW | T@lk  08:13, 7 May 2008 (UTC)

NICE guideline
The new NICE guideline advises coeliac serology in newly diagnosed irritable bowel syndome. It also advises screening in chronic fatigue syndrome. Torrent of new diagnoses? JFW | T@lk  07:32, 29 February 2008 (UTC)

Name (celiac not coeliac)
The more common name for celiac disease is "celiac" not "coeliac". I don't know why wikipedia has it spelled this way but I think that the name should be changed. The vast majority of website name the disease "celiac" not "coeliac". Bobje (talk) 22:46, 17 March 2008 (UTC)


 * It depends which part of the world you are in. The spelling coeliac is used in British and Commonwealth English. We have been through this before, see this discussion. On the English Wikipedia, once a page has been created under the British spelling it is not usually moved to the American spelling or vice versa. JFW | T@lk  01:13, 25 March 2008 (UTC)


 * How do we pronounce coeliac? OptimistBen (talk) 06:38, 16 April 2008 (UTC)
 * Different spelling, same pronunciation - like see-li-ac, emphasis on the first syllable.Trishm (talk) 11:21, 10 May 2008 (UTC)

LFTs
The following was added in "signs and symptoms":


 * An unexplained elevation in liver function tests may be the presenting sign of celiac disease in some children.

Firstly, this is not a sign or symptom but a laboratory abnormality. Secondly, while I have seen this mentioned in many publications, I am not sure whether it ever develops in the complete absence of any further symptoms nor am I convinced that this has been particularly well studied. JFW | T@lk  01:13, 25 March 2008 (UTC)

History
is another historical resource (BMJ 1988). JFW | T@lk  11:27, 31 March 2008 (UTC)

Neurocoeliac
Another neurologist who doesn't believe all those papers associating coeliac with certain neurological presentations. Lovely rant about EBM: JFW |  T@lk  22:07, 9 April 2008 (UTC)

Main Page?
Apparently, May is celiac disease awareness month in the U.S. This fine article hasn't been on the Main Page yet—how about putting it in the queue when there's an opening? Fvasconcellos (t·c) 23:30, 9 April 2008 (UTC)


 * Will do. JFW | T@lk  11:26, 11 April 2008 (UTC)


 * Is on TFAR for 22 May: diff. JFW | T@lk  08:05, 7 May 2008 (UTC)

Genetics - more
is a genome-wide study from Nat Genet. Sounds like we will need to cover this, but I have no access to the journal. JFW | T@lk  11:22, 11 April 2008 (UTC)


 * I have the paper, coincidentally DLed it this morning, I will need to go over it with a fine toothed comb. Basically, the authors argue that all sites identified are already associated with autoimmune disease. The question is whether any of these associations might be secondary to celiacs or are they shared associations. Pdeitiker 15 April 2008 (UTC)


 * Given that you seem to have the paper, could you work its conclusions into the article in a brief, clear and comprehensive way? The level of detail in the below subsections is not really possible I'm afraid. JFW |  T@lk  08:05, 7 May 2008 (UTC)


 * I am hesitant to do that with this paper. I am concerned that the study is biased by the diagnoses that leads eventually to the coeliac diagnosis. I do not see that they have picked the study subjects from assymptomatic population.Pdeitiker (talk) 13:55, 20 May 2008 (UTC)


 * Subpage for genetics?Pdeitiker (talk) 13:28, 21 May 2008 (UTC)

The paper
Hunt et al. Newly identified generic risk variants for celiac diease is relate to the immune response. Nature Genetics 40:395-402Pdeitiker (talk) 02:00, 16 April 2008 (UTC)

The case for 1q31 (putative RGS1)
The putative locus is the regulator of G-protein signaling 1 - rs2816316 location. Corroborrating Evidence -
 * Increased B-cell translocation in mice
 * Chemokine stimulated dendritic cell activity
 * localized in small intestinal biopsies
 * mouse intraepithelial cells.

With regard to this rs2816316, the authors give an overall P of 2.58 x 10e-11. The odds ratio is 0.71, although the allele frequency in CD of major and minor alleles is not apparent in the paper. There appears to be a marginal Type 1 diabetes association with this locus at p = 0.03. Confusing was the WTCCC table given that shows CD (referring to Crohn's not celiac disease. In the WTCCC table two alleles A and G were given, in the supplimentary material of A and C were given as major and minor variants (Celiacs = 0.1362-"C" and Normals 0.1741), therefore the minor allele is less common in celiacs. In T1D assuming that there is just a typographical error there is a similar decrease in the minor allele "C". If the information is correct then the distribution of homozygotes of A/A should be higher in celiacs.

The case for 2p21-22 (putative IL18)
The statistical case for this allele is much stronger. Crohn's disease is modestly associated with the same locus. IL18 induces T-cells to produce inteferon. The alleles are rs13015714 and rs917997 for genome wide markers.


 * IL18RAP is expressed in natural killer cells (what kills the epithelial cells?)
 * expressed in intestinal biopsies
 * IL18 is expressed in mucosa of active, treated and latent celiac disease but not healthy controls.

The WTCCC (Nature 447: 661-678) found the allele B ("T") to be associated with Crohn's disease (p=0.0008) and examining their data I came to a similar conclusion. There is a marginal risk for a type II diabetes association. rs917997 in celiac disease paper is given as A1 (minor allele) as "A" and major allele as "G". These rs markers generally only recognize one SNP so which is correct C/T (102508428) or A/G (102437000). These differences appear to be the result of a slight shift in SNP used by 71400 nt (or not). 102508428 is a physical map location. Therefore it seems to me there are errors in this paper that the authors have overlooked. The minor allele in which is higher in celiacs is also higher in crohn's disease.Pdeitiker (talk) 22:35, 15 April 2008 (UTC)

The case for 3q25-26, 28 (Putative IL12 and LPP)
rs17810546 and rs9811792 is a large linkage disequilibrated block may show an association with celiac disease. The region is proximal to IL-12 A locus (IL12A) IL-12A produces one subunit of a heterodimer that forms IL12p70.
 * broad range activities on T and natural killer cells.
 * induces T-helper cells. T-helper cells recognizing gliadin/HLA-DQ2.5(or DQ8) bearing APCs are a hallmark of celiac disease.
 * an LPP gene exists also the region. LPP is expressed in the small intestine.

The WTCCC showed no disease association with common autoimmune diseases. The rs9811792 shows an almost balanced frequency of two alleles in the population, rs17810546 has a minor allele that is 4% higher in the celiac population than in normals. Homozygotes of the minor allele are expected to be twice as frequent in celiacs compared to normals, but they would make a minor subset of the total celiac population. p-values for markers in the region of these two markers are low with minima in the 10E-9 range. The entire region appears to be linked or in strong long range linkage disequilibrium.Pdeitiker (talk) 22:34, 15 April 2008 (UTC)

The case for 3q21 (CCR cluster)
The marker rs6441921 is within the Cytokine receptor gene cluster (CCR1, CCR2, CCR3, CCRL2, CCR3, CCR5 and XCR1). It has been previously linked to Type 1 diabetes in the WTCCC study at p=10E-5 range. There is a pretty hefty increase in the homozygotes of the minor allele in T1D, which is something that molecular geneticists really like to see. For coeliac disease the minor allele is about 5% higher in the population than normals, with a p value of <10E-6 when all studies are combined. T1D and coeliac disease share about the same risk. The minor allele is increased by 14% in celiacs, and homozygotes (rare-11% in celiacs) by 30%. There is a potential, at least, for this to be an important marker in individuals who have both CD and type 1 diabetes. Pdeitiker (talk) 22:34, 15 April 2008 (UTC)

The case for 4q27
The authors have reported on 4q27 and the results have been integrated into the main page. Since that time the locus has found to be associated with Graves, T1D and Rheumatoid arthritis. The WTCCC gives a relatively strong association with RA. The genes located in the region are IL2 and IL21.Pdeitiker (talk) 22:41, 15 April 2008 (UTC)

The case for 6q25
The HLA locus is found on the p-arm, this locus, rs1738074, is on the q-arm, and for all intents and purposes segregates independently of HLA-DQ. In the WTCCC there is a marginally increased risk for Crohns, Rheumatoid arthritis and Type 1 diabetes. The SNP is found within a long segment of DNA under linkage disequilibrium. The marker was found in nearly balanced frequencies indicating selection is either balancing, variable, or neutral at the site. Since the neither allele frequency is low homozygote differences on either side represent only modest differences. The authors speculate on the TAGAP gene and product.

The case for 12q24
This locus has a surprisingly high association with type 1 diabetes for the marker SNP rs653178. The markers map to the region of SH2B3 (LNK) and ATXN2 with linkage disequilibrium over a region of 1 Mb (In comparison Super b8 which contains HLA-DQ2.5 in europeans) maps to almost 2.5 Mb. The link to T1D is relatively strong at 10E-13 in the WTCCC study, with homozygotes "C/C" about 50% more frequent in T1D. The case is less strong in celiac disease, with less than 10% change in the minor allele frequency. Also linked to this locus marginally are rhuematoid arthritis and crohns disease.Pdeitiker (talk) 01:39, 16 April 2008 (UTC)

Previously described loci and other loci
"CELIAC2 (5q31-q33 - IBD5 locus), CELIAC3 (2q33 - CTLA4 locus), CELIAC4 (19q13.1 - MYOIXB locus), have been linked to coeliac disease. The CTLA4 and myosin IXB genes have been found to be linked to coeliac disease and other autoimmune diseases.[37][38] Two additional loci on chromosome 4, 4q27 (IL2 or IL21 locus) and 4q14, have been found to be linked to coeliac disease.[39][40]". With the exception of 4q27 (added by the same authors) none of the other loci were recognized in this study. Therefore these studies appear to be largely at odds with each other. The only agreement that is universally found is for the HLA-D locus (DQ2 and DQ8 with the lions share of risk for DQ2.5cis haplotype). In addition to these studies, there are 2 ongoing studies that are looking at specific family related disease risk in Finland (15q11-q13) and other parts of Scandinavia (5q31-33). In the case of the Finnish study some speculation can be made that the disease may be traced to a single individual in the 16th century. Other studies have shown risk specific for Spain and Italy. The northern European population, particularly the Irish have very high levels of HLA-DQ2.5, 1/3rd of all Irish have DQ2.5cis and in certain western Irish counties that rate may be as high as 50%, up until recently the consumption of Triticum sp. was relatively low compared to other parts of Europe. There is a continuity of genetic relationship between the Irish, Western England, Scotland and Scandinavia which represents, probably, the retention of pre-Neolithic traits as a result of the northern extent of Triticum cultivation up to the bronze age. As a result these studies may be picking up genetic risk common to people of relatively common ancestry to the early holocene. Admixture within these data sets may be diluting risk factors evident in other data sets. Examination of the Irish in this set showed many associations did not hold up, indicating the opposite, that admixture (Nordic/islandic into continental) may be increasing risk in UK and dutch populations. For example, 1q31, 2q11, 3p21, 3p28, and 12q24 showed no association in the Irish, whereas 4q27, 3q25, 6p21 (p<10E-80) showed strong association and other sites, chr3 (rs1021701), chr7 (rs269243), chr9 (rs1952461), chr11 (rs10501723, rs6483061, rs7479104), Chr12 (rs2078178).

What we need to keep in mind is that the odds ratios are very close to 1 for the 'celiac' allele in these studies. This indicates highly contingent associations with other genes, environmental factors, or study biases. Following these traits in families may be more enlightening since as in the case of 3p21-28 linkage disequilibration could hold a nest of associated traits for historically relevant generations.Pdeitiker (talk) 02:43, 16 April 2008 (UTC)

Some thoughts
One of the enigmatic questions of coeliac disease is if coeliac is primary to autoimmune diseases then those autoimmune diseases should undergo remission on a gluten-free diet. The risk associated with gluten consumption and celiac disease is a bit of a rarity in that removal of gluten generally causes the decline anti-transglutaminase activity. It should be expected if tTG is involved in the presentation of other self proteins, then the severity of other autoimmune diseases should abate, however abatement seldomly occurs. One plausible answer to this question is that other autoimmune diseases occur in CD with tTG assistance, but in these instances there are other promotors of disease, such as genetic risk factors. In this way, once a certain threshold is crossed these other autoimmune diseases have sufficient other factors to maintain themselves. We can also flip the argument, some of these markers, with the direction of allele association similar to CD, may be apparent in this data set because the second autoimmune disease was detected first and lead to the detection of CD. Since most CD goes undetected, having a secondary disease that has its own associations brings those associations into the CD genetic association. To remove this bias, CD needs to be selected from a population of randomly screened individuals for CD. The paper (Hunt et al. Newly identified generic risk variants for celiac diease is relate to the immune response. Nature genetics 40:395) was extremely difficult to comb through the data, there were many dangling abbreviations in the supplimentary information, its going to take some time to digest completely their methods before I would be willing to alter the genetics section. One problem of course is what to do with the other, older, studies.Pdeitiker (talk) 01:54, 16 April 2008 (UTC)

Pathophysiology section
" Almost all coeliac patients have an abnormal HLA DQ2 allele.[1] However, about 20–30% of people without coeliac disease have inherited an abnormal HLA-DQ2 allele.[24] This suggests additional factors are needed for coeliac disease to develop. Furthermore, about 5% of those people who do develop coeliac disease do not have the DQ2 gene.[1] "

I don't mean to be nitpicky, but there is ___no___ evidence that DQ2 is abnormal, in fact in certain parts of Africa it is the predominant allele. The statement above, IMHO, infers an ethnocultural bias that alleles or genes that are reactive to western foods are some how defective or abnormal. DQ2 frequency in certain parts of Europe is around 45% far higher than any other alleles in those regions. This high rate of gene frequency can be attributed to past positive selection, particularly in the pre-Neolithic period in Europe.

DQ8 reaches a gene frequency of ~80% in some populations. This is the highest gene frequency for any DQ type seen in any other people in the world. It strongly indicates positive selection. Both DQ8 and DQ2.5 are acid peptide presenters, and both have been found in regions of the world were shellfish consumption (as identified by the archaeological record) was quite common. IOW these may have been positive adaptations for a different kind of diet.Pdeitiker (talk) 12:48, 22 April 2008 (UTC)


 * I know that you have elaborate theories about this, but all this comment does is cite a reliable source. I am against changing this in favour of some paleogenetic inference. JFW | T@lk  08:05, 7 May 2008 (UTC)


 * See ......Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20753-8. Epub 2007 Dec 17. Recent acceleration of human adaptive evolution. Hawks J, Wang ET, Cochran GM, Harpending HC, Moyzis RK.

" (iii) an implausibly high number of adaptive substitutions [in these disequilibrated regions] between humans and chimpanzees, and (iv) nearly 100 times the observed number of high-frequency linkage disequilibrium blocks. Larger populations generate more new selected mutations, and we show the consistency of the observed data with the historical pattern of human population growth. We consider human demographic growth to be linked with past changes in human cultures and ecologies. Both processes have contributed to the extraordinarily rapid recent genetic evolution of our species. "

There are a number of papers on HLA that have stated that DQ2.5 was under positive selection in the past, but is under balancing selection, now, in some populations. It is called the European Ancestral Haplotype. If you need a body of references to change this opinion I can provide them. In the Hawks paper, the super B8 haplotype is longer than the longest haplotype they were capable of identifying, without selection would be 100s of years in age, but in fact by its distribution appears to be 1000s or 10s of 10000s of years in age. In theory all high frequency HLA should be under balancing selection but DQ2.5 is the only hap that has a measurable decline, most probably because of coeliac disease. Pdeitiker (talk) 13:04, 20 May 2008 (UTC)

Here is a review on the matter: doi: 10.1111/j.1744-313X.2008.00765.x International Journal of Immunogenetics 35, 179–192 179 Human MHC architecture and evolution: implications for disease association studies. J. A. Traherne

" Recent global studies using long-range haplotype (LRH) and extended haplotype homozygosity (EHH) tests support the hypothesis that signatures of positive selection are present in the MHC (The International HapMap Consortium, 2005, 2007; de Bakker et al., 2006b; Voight et al., 2006; Sabeti et al., 2007). " " Two of the most frequent long-range MHC haplotypes in Northern Europeans are the HLA haplotypes HLA-A1-HLA-B8-C7-DR3-DQ2 (also termed AH 8.1) and HLA-A3-B7-C7-DR15-DQ6 (the so-called ancestral DR2 haplotype). The frequencies of these haplotypes in European Caucasians are in the order of 10%, which is substantially higher than expected (< 0.5%) based on the frequencies of individual alleles on the haplotypes. The high sequence similarity of long-range haplotypes suggests that their prevalence is likely due to significant expansions in relatively recent times. Indeed, the AH 8.1 haplotype has been estimated to have diverged from a single common ancestor about 23,500 years ago (Smith et al., 2006). "

I agree about the timing, but if the timing is correct, then the AH 8.1 (alias super B8) was either singly expansive or under stringent positive selection after expansion. Linkage disequilibrium of the haplotype is very high for a haplotype of 23 kya. I have also a recent paper on Type 1 diabetes that shows linkage in some instances can be extended to 6 million nucleotides (1 Mbp generally = 1 centimorgan, with expected equilibration times in 100s of years). The only way selection is not involved in AH 8.1 disequilibrium is if AH 8.1 was the only haplotype in western europe for 15 to 20ky. And yet other haplotypes in Europe also show similar disequilibrium and long term presence. AH8.1 LD factors into population spread as wide from the Irish to the Basque to the Swiss to the Scandinavians with no evidence of recent immigration of AH8.1. There is a "cassette" of 4 types with stable ratios between the ancestral types: AH8.1, A3-B7-DR15-DQ6.2, A2-Cw5-B44, and A2-B7-DR15-DQ6 (AH 8.1 and A3..DQ6.2 is modal in W. Ireland, A2-B44 is nodal in the Cornish, A2-B7 is nodal in the Swiss). This indicates a cline created in the post-meoslithic period from 4 ancestral types introgressed by a large number of haplotypes of Mediterranean and Black Sea origin. An anti-node is reached in the Paris basin in which AH8.1 is 1/5th as frequent as found in the Western Irish. AH8.1 had declined as a result of negative selection in the post-neolithic although it was a dominant and stable feature of NW Europeans prior to the Neolithic. This does not indicate an genetic abnormality.

" The estimated ages of some common long-range haplotypes typically fall within range of the human migration out of Africa and expansion into Europe. This has led to theories of selective factors that acted to expand these haplotypes, which in general relate to adaptation to new environments, changes in nutrition, or resistance to infection during migrations (Distante et al., 2004; Moalem et al., 2005). "

Indeed, and in the regions of Europe where AH8.1 is high now, and in which there is an archaeological presence there is a consistent appearance of shellfish within the diet. Despite the large presence of bovids and reindeer within Europe from the LGM until the mesolithic, at only a few sites are bone fragments found. All but one site shows the presence of shellfish, and human bones show a strong carbon isotope ration consistent with marine nutrient dependence. The mesolithic in western Europe extend from 6500 bp(average) to the ~10,000 years ago. The only reason one does not see more dependence on shellfish is that today sea levels are 120 meters higher than at the holocene boundary did not begin to reach current levels until 8000 years ago, and as a result most sites are underwater. [AH8.1 in Europe is the parent haplotype of DQ2.5] One reason why DQ2.5 may be so high in Ireland is that the full neolithic package such as found in LBK culture of loess belt was not viable in Ireland, cattle pastoralism and barley cultivation did take root, but so did millet cultivation. Barley is the least related grain to wheat and preserves few pathogenic epitopes, it was malted and fermented, lowering its toxicity even more.

" Any past survival benefits of common long-range haplotypes have come at a cost since many predispose to inflammatory diseases prevalent in Westernized society, such as type I diabetes and multiple sclerosis. "

Many recent papers strongly agree with this conclusion. The results of the human genome project and the HapMap are parsimonious with this as a general background for the increases in autoimmune diseases as people transit from indigeonous cultures into westernized cultures. This does not infer that previous traits are abnormalities, since they confer selective advantages in specific regions. This in and of itself warrants a change in how the section is worded. In fact, given that that AH8.1 is ~ 23,000 years in age and the neolithic did not reach the node of AH8.1 (W. Europe) until a few thousand years ago (Liberally: Thracia 10 kya, Balkans 8.5 kya, Italy 8 to 9 kya, Iberia & Austria 7.5 kya, Germany, Netherland, Paris basin 7 kya, S. England 6.9 kya, Ireland 4.3 kya), there is no reason to believe that AH8.1 was disgenic when it formed or spread in Europe.Pdeitiker (talk) 19:04, 23 May 2008 (UTC)

Tartrazine
This article is missing any reference to the theory that those with celiac disease also have an intolerance to Tartrazine (Yellow food dye 5). I'm not sure if the intolerance to gluten and tartrazine are caused by the same bodily reaction, but every person I know with celiac (Several dozen) disease has a bad reaction to tartrazine so I assume they are linked. - 99.251.77.247 (talk) 01:10, 26 April 2008 (UTC)


 * There are a number of suspected damaging agents that could potentially trigger conversion to pathology or symptomacy in celiac disease. The list of suspected agents is long, for example rotavirus, enterovirus, influenza virus, aspirin, NSAIDS, MSG, sodium benzoate, certain food colorings, heliobactor pylori. With respect to the chemical agents it is known that aspirin and NSAIDs can 'pock' the small intestine and stomach with lesions which under appropriate conditions can allow food peptides (partial digests) to enter the blood stream thereby causing peripheral allergic responses. Such responses are seen in Urticaria, Schleroderma and are similar to exercise induced anaphylaxis in which, for wheat, the antigen, omega-gliadin, has been determined and the response pathway involves Mast cells, eosinophils and IgE. The chemicals may play a role in idiopathic gluten sensitivity, such as gluten sensitive idiopathic neuropathy or gluten sensitive autism. I have CD but I show no special reactivity to FD&C yellow#5, however I have a relative with strong wheat allergy (not CD) who does. OTOH, while I show no particular reactivity to aspirin or NSAIDs I choose to avoid taking these substances because of the potential risks that are elevated in celiacs.
 * One particular facet of celiacs is they frequently have intense wheat allergies as well as intolerance particularly after entering a GF diet. Allergies can be distinguished from CD because of the reactivities to HMW glutelins, omega-gliadin, and non-glutinous proteins. Some who have not been diagnoses and claim to have CD actually have a wheat allergy, others have both.Pdeitiker (talk) 13:20, 27 April 2008 (UTC)


 * I think 99.251 was looking for a reference. The University of Chicago website is quite clear that tartrazine is safe. Pubmed gives no results for "tartrazine celiac". I think this concludes the matter - an assumption of linkage would be WP:NOR. JFW | T@lk  08:05, 7 May 2008 (UTC)


 * The health effects of Tartrazine are pertinent to CD and many celiacs have spoken of sensitivity to this. Not that it warrants lengthening this page, however it might be worthwhile addition to one of the subpages. The problem I have with the tartrazine issue is classification, because it is unclear whether it is a specific factor in CD versus allergic diseases. Or to put this in another light, in a very few people tartrazine may increase risk for CD, CD symptoms after latent disease, in others allergies, or in others sensitivities and intolerances. Finding triggers for autoimmune diseases is like picking a needle from a haystack, can chemical "E102" be the trigger, or does the sensitivity show up after the disease is present WP:NOR?Pdeitiker (talk) 13:27, 21 May 2008 (UTC)

Some APT papers

 * 1) Level of gluten consumption tolerated is highly variable, but <10mg/24h is unlikely to lead to symptoms although some develop mucosal abnormalities on amounts just slightly higher than this - systematic review
 * 2) European stakeholder research agenda
 * 3) Serology is so good that endoscopy is a waste of time (yes, still controversial) -
 * 4) Dermatitis herpetiformis may cause villous atrophy, but is not associated with osteopenia, fracture or malignancy. At the same time, it seems to protect against breast cancer (and coeliac disease does too!) }

I'm not sure if all of them need inclusion, but 1. perhaps should. JFW | T@lk  08:05, 7 May 2008 (UTC)


 * Before anyone asks, the DOIs are not activated yet (Blackwell being slow). Simply google for the DOI, and it will show up. JFW | T@lk  08:20, 7 May 2008 (UTC)

Autoimmune
Coeliac disease isn't an autoimmune disorder. Autoimmunity is an inappropreate response to self - I think it's fairly from the effect of diet, the antibodies produced and experiments from mice that the response isn't to self, it's to the contents of the gut, specifically wheat products. It's probably better to say it's an Immune-mediated disease Kantokano (talk) 17:08, 18 May 2008 (UTC)


 * Anti-gliadin T-cells recognize human-tissue-transglutaminase covelantly linked to gliadin (wheat) peptides. The T-cells stimulate human transglutaminase specific B-cells. This results in producing anti-tTG antibodies. The allows the targeting of connective tissue by eosinophiles (Eosinophilic gastrointeritis is a common finding in CD) and the targeting of surface tTG on epithelial cells by natural killer cells which results in the destruction of the villi. This causes villous atrophy. Therefore CD is an autoimmune disease. Pdeitiker (talk) 13:10, 20 May 2008 (UTC)


 * I agree with Phil that coeliac disease has all the features of an autoimmune disorder, except the precipitant for molecular mimicry is actually well understood (as opposed to many other autoimmune disorders). There is evidence of an autoimmune diathesis in coeliac disease. JFW | T@lk  06:09, 23 May 2008 (UTC)

Vegiac
I have asked to justify the inclusion of the long paragraph on vegetarianism. The reference provided is from a low-impact journal, and on PubMed there is no research on the gluten-free diet in vegetarians. I'm sure the problem exists, but in the absence of reliable sources there is little we can do. Discussion about Vegiacs and its coinage seem to be WP:WEIGHT - this is about one website. JFW | T@lk  06:11, 23 May 2008 (UTC)

Source worth including
is a recent (2006) update for pathologists. Given that it is free (J Clin Pathol) we might be able to include it preferentially. JFW | T@lk  08:59, 3 June 2008 (UTC)

A-2 Gliadin 57-89 "33mer" studies
There are two recent papers, Moron et al. 2008(PLOS one) and Moron et al. 2008(Am J. Clin. Nut).

The 33mer of gliadin, which the authors paint as being quintessential T-cell epitope in gliadin, is used to develope 2 monoclonal antibodies(Mabs). The Mabs are then used to probe the level of wheat levels. The Mabs do recognize gliadin but recognize deaminidated gliadin a > 1 magnitude lower, in both cases. Monoclona1 antibody A1 recognizes also the innate peptide region "19mer". While the antibodies do recognize the major cluster of T-cell epitopes (Coeliac disease is a T-cell mediated autoimmune disease) that cause celiac disease, they appear not to recognize the same structures as T-cell receptor/HLA DQ2.5 complex. So that these antibodies can not be seen as equal to this complex recognition. The basic outline of the first paper is that by having tools that can detect the two most important sites of gliadin, that they have effective tools for diagnosing disease or therapeutic methods.

Having said that the antibodies recognize and discriminated binding of rye secalins and barley hordeins with high affinity with at least one of the Mabs, protein to protein in some cases higher than gliadin. Both antibodies to oats appear to shadow the wheat A1-G12 differences suggesting that this reaction could be due to contamination of wheat with oats. Recognition of oat avenin is 2 magnitudes lower consistent with other studies. They constructed peptides corresponding to sites in gliadin, secalin, hordein, and avenin. The monoclonal antibody to A1, based figure 5E does not appear to have a significant response to oats given assay point variance. This indicates an apparent advantage of using synthetic peptides over native proteins that can be contaminated from their source. One could argue that there is not enough sequence information from oats or they used sequence from a non-CD causing oat strain.

They tested the effectiveness of these antibodies on digesting whole wheat bread in synthetic stomach acid for 1 hour using 2 therapeutic enzymes pepsin with EP-B2 and SC PEP (neither of which are defined in the paper) but apparently cut at prolines and glutamines. They show that either alone will only reduce the 33mer. The problem here is that some stomach fluid will leak out an one hour and the bread (1 gram - a real meal!) was premixed with the enzyme before addition to the stomach acid.Pdeitiker (talk) 01:54, 10 June 2008 (UTC)


 * I just wanted to add that I read the materials and methods of both papers, and they gave no mention in either paper of having drawn an especially selected batch of oats that was wheat, barley and rye free. The assumption is that these are off the shelf or out of the bin oats. Here is an instance where it is preferential to use the synthetic peptide data over the protein digests because the later is at greater risk of contamination.Pdeitiker (talk) 03:22, 10 June 2008 (UTC)

Dietary guidelines ..
For a paper written in 2005 it gives a surpisingly balanced perspective on diet. This paper has been referenced up the page- - Kupper. Gastroenterology 2005: 128, S121-S127.

Oats
Oats are single-handedly set aside from wheat(spelt, semolina,durum), rye, barley, triticale and kamut in this review as they are controversial. As part of that they come to no opinion about oats other than the results, as of 2005, were premature. As I mentioned two papers provide 5 year followup on children and adults who eat oats, no disease was seen in the patients which did not intially react with oats, although the reason why 2 patients in the study dropped out was unclear. They stated that contamination varied, a common observation, from <1.5 ppm to >400 ppm. Here is what kupper says:

"'Research supports that oats may be acceptable for the majority but not all patients with CD. Ludlin at al. also suggests that there may be a subset of CD patients who have an exaggerated sensitivity to oats, not related to CD'(Kupper, 2005, gastroenterology 128, S122)" In essense we are in complete agreement. I have seen figures thrown out that oat intolerance represents 10 to 20% of CD, and others suggesting 1 to 5%. It is clear that a subset of celiacs are completely tolerant of GF oats, however not enough studies have been done, the currents studies lack, technically, statistical power. She goes on to say:

"'At this time, there are no large-scale studies available to assess the potential contamination of commercial oats'(Kupper, 2005, gastroenterology 128, S122)"

See:Oat contaminants in Europe Canada and US

The reward may outweigh the risk.

"'Storsrud found that the use of oats increased the patients intake of iron, dietary fiber, thiamin, and zinc'(Kupper, 2005, gastroenterology 128, S122)"

Pdeitiker (talk) 01:54, 10 June 2008 (UTC)

Wheat Starch
One of the key issues of the paper is wheat starch. For a bit of background information it was found in 1952 that the starch fraction of wheat could not maintain disease in children, whereas the protein fraction did cause coelaic disease. This was the critical breakthrough in gluten-sensitive enteropathy, since previously it was believed that cereals did cause coeliac disease. The guidelines point out that wheat starch, when properly purified to standards contained only trace amounts of gluten, and in fact the protein estimate is a high end estimate of gliadin since it is certain contaminated with other endosperm proteins.Pdeitiker (talk) 16:48, 11 June 2008 (UTC)

Anti-yeast antibodies (ASCA)
A new paper has been published in the J. clinical immunology. The authors examine 242 suspected celiacs for presence of antibodies to yeast, Baceroides caccae ounter memberane protein, and Psuedomonas fluorescens I2 sequence. What they found is that of the 242 suspected 134 were confirmed of these 62 (47%) has ASCA, whereas of the non-CD in the suspected group only 15% showed ASCA. The reactions with either B. cacae Omp W or P. floursescents I2 sequence were not significantly different between the CD and non-CD within the suspected cohort, although the reaction with I2 was slightly higher. The presence of ASCA, anti-OmpW or anti-I2 was higher in the suspected group even if no CD diagnostic was made relative to control. This suggests that some sensitivity to wheat in the form of breads and other risen foods is due to inflammation caused by ASCA. ASCA has been associated with Crohn's disease and a form of microscopic colitis, people with ASCA may have decreased lectin binding proteins, and the site of inflammation is typically the ileum and ascending colon. Both diseases are a form of inflammatory bowel disease. Pdeitiker (talk) 21:27, 10 June 2008 (UTC)

Celiac disease in the Elderly
There is a recent article from Finland outlining the incidence of coeliac disease specifically in the elderly group. There are some interesting finds in this paper. One find is that the group born before 1930 had the lowest risk of celiac disease 1.48% at age ~80 ya. The younger groups (~70, ~60)had 2.4% incidence of celiac disease. Of the 2815 people screened 25 had appeared positive at or before the onset of the study and 6 presented with DH, 4 became positive after the study began, all classified were Marsh grade III. 49 of 2815 had ATA IgA, 44 were EMA positive. A total of 60 patients together showed clinical signs. 2 additional subjects who did not undergo biopsy were included as positive, bringing the overall frequency to 2.45%. This frequency is much higher than the 1% frequency often cited for the general population. Of 38 seropositives all had DQ2 or DQ8. Of the 35 detected in the screening, 20 (57%) had no gaastrointestinal symptoms. The primary symptoms in those picked up by screening were abdominal pain & distention, flatus and infrequently diarrhoea or loose stools. Whereas those detected clinically diarrhoea and maladsorption were the most common symptoms. 2 of 60 had EATL that appeared without refractory celiac disease (called 'de novo' WS- EATL ). In one case, the individual had CD for 27 years. Of those picked up in the screening 25% had autoimmune thyroid disease, 3 had psoriasis, one had type 1 diabetes, and 1 had pernecious anemia. 28 of 32 who went on GFD reported improvements in symptoms, 6 reported marked improvement. 87% had a significant reduction of Marsh score, the median being Marsh grade I and serological scores of 31 showed only 2 with positive scores. These criteria indicate that there was an increase in CD incidence with aging, this was shown by biopsy, serology, genetic testing, and the restoration to normality on the GFD. The results suggest that lifelong risk of celiac disease is higher than 1% frequently given, if the DQ2:DQ8 ratio in CD remains constant with age, then it is likely that a significant fraction, ~12-20%, of DQ2.5 positive individuals will have gluten sensitive enteropathy within their lifetime.Pdeitiker (talk) 22:40, 10 June 2008 (UTC)

Oat contaminants in Europe, Canada and US
This paper I mentioned above, it is fairly complicated, as I have read it now 3 times, somewhat grasp what they are trying to prove. Most current tests for gluten look for gluten - by definition gluten is the sticky proteins in wheat that form the gluten aspect of bread making. In reality, this generally includes all glutinous proteins but for gluten free diet it refers to glutinous proteins in wheat, barley and rye. Based on immunochemical understanding, once disease is present, all members of Triticeae are likely to restimulate CD. Therefore testing for wheat gluten, only, in oats is not thorough. The paper Hernando et al. looks at 134 oat sources, they use an R5 sandwich assay that detects wheat, barley and rye. The authors do not state, nor should the reader assume that the R5 ELISA is a measure of T-cell immunoreactivity, only that the assay has detected glutinous material from three species. The second approach that they use is Q-PCR to determine whether barley, rye or wheat DNA is present. Western blot is also used as well as Maldi-TOF Mass spectroscopy.

As suspected many oat varieties (supplied by various hospitals) showed up with contaminants. In this paper finding out the source of contamination requires some work. For each source, say V12-from the US, there are several samples (e.g. 11 for V12). Some of the samples were oat berries, the oat berries were covered with dust, and the dust could be removed with an alcohol wash. The dust on 3 samples was the source of the contamination. The pure oat strains did not show western blot reactions with R5 antibody. The problem in examining the blots is that few of the patterns, obviously contaminants, match reliably wheat, barley or rye patterns in the control. In the US, the Q-PCR reveals that wheat, then barley are the primary contaminants. One sample, 106 from Finland had abundant contamination (I estimated 22%). The DNA suggested that barley was the primary contaminant, and by MS-maldi one can see barley proteins comparable in abundance to avenins, the level of barley contamination suggested this grain was a mixture of oats and barley. 97% of the contamination of this was barley and the barley pattern was apparent on the western blot.

The paper goes on to discuss the medical-political situation with celiac disease. The fact that US and Canada have not recommended oats in diet is something they concur, that oats are not safe for celiac consumption until the sources of Triticeae within the potential contaminants can be measured. They recommend their test-method, but also suggest that the method alone is not sufficient, that western blot, and PCR should be performed or maldi-MS to look for evidence of contamination. We also see, that with many papers that give immunochemical reactions to oats may not have carefully looked at all sources of contamination from Triticeae cultivars and wild grasses. They go on to say "It may, however, take some time before gluten-free oat-based foods are totally accepted and oats are removed from the list of toxic cereals". Pdeitiker (talk) 05:02, 11 June 2008 (UTC)

What happens after diagnosis?
This page summarily states that in the vast majority of cases, all symptoms resolve. The review cited does not appear to be focused specifically on post-diagnosis. I feel like the truth may be more complicated, and several papers back me up this, but I'm having trouble finding reviews.


 * Those quality of life issues are not so well appreciated, as we can see above. But there are limitations on the most effective size of this page. —Preceding unsigned comment added by Pdeitiker (talk • contribs) 22:05, June 14, 2008

I put together a list of PubMed abstracts; they're pretty evenly divided on the quality of life and results after diagnosis. I think this deserves more attention in this article. ImpIn | (t - c) 12:12, 14 June 2008 (UTC)


 * Some of, or similar pubmed links are referenced there. You can add information or please create a new section in the talk page.
 * As you can see there is too much associated disease to mention on this page.
 * As you can see there is too much associated disease to mention on this page.

Pdeitiker (talk) 22:05, 14 June 2008 (UTC)


 * The article says no such thing. Diarrhoea and digestive system symptoms tend to improve a lot. The article quotes a good study that says that many people continue to experience symptoms. Also: we cannot possibly cite all the articles you are referring to. Could you identify a free article with a wide scope? JFW | T@lk  09:14, 15 June 2008 (UTC)


 * In fact, (which is in your list) is already being cited and discussed. It is the best of the 13 papers you have linked. JFW |  T@lk  09:26, 15 June 2008 (UTC)

He did not provide a proper link. Here are the articles he linked to (see edit page):

" I put together a list of PubMed abstracts; they're pretty evenly divided on the quality of life and results after diagnosis. "


 * 18372595-
 * 17644056-
 * 18372595-
 * 18176960-
 * 14624151-
 * 17305757-
 * 12088289- " Concerns about the burden of a gluten-free diet, at least over the short term, may be unfounded."


 * 14705832- Precise information that suppliments information on GSEAC page?
 * 18176960- GastroIntest Quality life index better in patients on a GFD than in non-treated patients. "Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status."
 * 17470666- To be added to associated conditions page.
 * 9759948- Need more details.
 * 16772832- 23% did not adhere to GFD to explain some symptoms
 * 11346203- reference 86 below

Here is a selection from GEA Associated conditions:


 * "Alopecia areata
 * GSE has been found to be associated with alopecia areata (patchy baldness) [44] whereas regrowth did not necessarily occur on a gluten free diet. [45][46]"


 * "Diseases of the pancreas, gall bladder, bile duct
 * Primary biliary cirrhosis. CD is prevalent in primary biliary cirrhosis (PBC)[67][68]. In PBC anti-mitochondrial antibodies are directed toward 3 mitochondrial autoantigens (pyruvate dehydrogenase, oxoglutarate dehydrogenase,branched-chain alpha-keto acid dehydrogenase), 2 or more nuclear proteins (nucleoporin 210kDa, nucleoporin 62kDa, centromere protein, and sp100), and 57% of acute liver failure patients have anti-transglutaminase antibodies."


 * "Depression
 * Depression in GSE has several causes, in the more severe CD depression can be the result of lower vitamin adsorption[10] and essential fatty acid adsorption (see section on autism). Depression and anger may also be the result of lower quality of life issues as a result of gluten-free diet.[85] Depression appears to persist on gluten free diet in a sizable fraction of GSE.[86] Elevated anger has been noted also with GSE."
 * This particular aspect is backed up by a half-dozen references, if not more.


 * "Anxiety
 * Anxiety is a common feature of GSE, treatment on a gluten-free diet is effective at reducing anxiety, some aspect of which may be due to maladsorption phenomena and cytokine activity (i.e. constant stress). More resolution of anxiety is expected on gluten free diet.[86]"
 * This one is to be corrected with new information.


 * Dump from other article refactored


 * And returned.

And others, it goes on to mention refractory disease, RCD2, EATL, etc. Pubmed of celiac diease produces 14,000 papers, the associated conditions article has 116 references.


 * Yes, and you've done a great job at being rather unselective. Not everything that appears in print is relevant for a general encyclopedia. I have taking the liberty of refactoring a sampling of gluten-sensitive enteropathy associated conditions.


 * Yes and it was returned, this is a talk page. I agree that most of the abstracts he presented were not worthy on either page, but implying that less than 1:100 articles are worthy of referencing here is not justified.Pdeitiker (talk) 16:54, 16 June 2008 (UTC)


 * To be more precise: just because someone cobbles together a few case reports on "wow, a rare condition in someone with coeliac" doesn't mean it needs citing here or anywhere on Wikipedia. When strict rules on clinical causation are applied, the links are often flimsy in the extreme.
 * I believe I have cited, above, an article rather critical of the concept of "neuro-coeliac". JFW | T@lk  16:15, 16 June 2008 (UTC)


 * To be more even precise: link to the paper you cite again, so it's more clear. There are lots of links flying around. Are you referring to, which you said was the best of the 13? Here's what that says:

I don't see a lot of evidence for this assertion that "in the vast majority of cases all symptoms resolve". I'll be looking into improving the section at some point. ImpIn | (t - c) 22:48, 16 June 2008 (UTC)


 * But how selective were those clinicians in excluding oats from a gluten-free diet? One paper, no testing of quality? The restriction of oats from a gluten free diet was based on one study, that no-one else could reproduce in the 1950s, and yet you seem that this is the status-quo. This is a turf-war, not a good-science versus bad-science discussion.
 * We have got the citation of 6 genetic loci that other papers can't support. Should anything but HLA-DQ be in the genetics section.
 * A little more calm here is due. You may be surpised that some of those that have literary support were markedly reduced from selections (sometimes as many as a dozen papers in support). Whereas I see many articles on wikipedia, for example one article claimed that MCR1 in humans came from Neandertals based on one paper. I could have easily had multiple references in that pages with 1000 references cited in GSEAC.
 * I would also point out that most of these conditions I included in the page were picked up in discussions between celiacs, after which I investigated whether or not there is clinical evidence or not.
 * Why does this page spend so much time on meta-issues (like church positions), should not that bandwidth be devoted to more health related things. Aren't the religious issues "quality of life issues", why spend so much on church issues and so little time on persistent health issues that affect quality of life. Also the history section contains a number of cites that are ambiguous and weak, both the religious and history section need refactoring.Pdeitiker (talk) 16:54, 16 June 2008 (UTC)

Phil, while you are asking for calm you are continuously waffling on the talk page without making the slightest attempt to improve the article. That is starting to annoy me. You keep on dumping enormous amounts of text here, knowing quite well that nobody monitors this page apart from me and one or two other souls. Are you expecting a response? Or are you using this as your personal Reference Manager?

If you have issues with the oats question, please provide the right papers that address clinical questions and not studies on rat epithelium or somesuch. If you want the genetics content to improve, be bold. But stop lamenting.

Your parallels with the MCR1 article are WP:OTHERSTUFFEXISTS and I will not address them separately.

We are addressing church positions because this is a general purpose encyclopedia that deals with real-life issues beyond whether oats are safe etc etc. As an encyclopedia we need to be discussing the social dimension of scientific subjects in a way that medical textbooks would not ordinarily do. If the information is out there, and is notable, we should be dealing with it. I really don't understand what is so difficult about that. Similarly, the history section is just fine and you'd do best to keep your hands off it. JFW | T@lk  19:41, 16 June 2008 (UTC)


 * The free-access review Complications of coeliac disease: are all patients at risk? gives an expert overview of the topic. See the section on "Quality of life", where it states that in one survey 77% of patients had improved quality of life after diagnosis, but that anxiety and depression are still relatively common. Tim Vickers (talk) 20:46, 16 June 2008 (UTC)


 * "the history section is just fine and you'd do best to keep your hands off it"
 * "deals with real-life issues beyond whether oats are safe etc etc"
 * "please provide the ***right*** papers that address clinical questions and not studies on rat epithelium or somesuch" [Who determines for this page what is right?]
 * Truth lies at the intersection of valid perspectives. The more valid perspectives we have on the truth the more likely we are to know where truth can be found. Pdeitiker (talk) 22:03, 16 June 2008 (UTC)


 * QOL issues are out there, they have been discussed here, although they are underrepresented on this page. I did create a page on Oat sensitivity, that removed some of the pressure on the The oat controversy, which is on two pages. I suggest you read the section, you may find your 'stardard' is about to change.
 * P.S. I think that it is particularly unfair that a standard based on one or few poor studies become the 'null hypothesis' that somehow needs to be disproven. I also know what celiacs are discussing, and one of the major issues are recurrent conditions on GF diet.

Pdeitiker (talk)

You don't need to quote my words back at me. Wikipedia is not about WP:TRUTH. It is about consensus. There is no consensus on any of the topics we have been discussing, because I cannot agree with your insistence on making such a fuss over oats and genetics, and I certainly cannot agree with your suggestion that the "social issues" and "history" sections should be curtailed. I think it would be helpful if we worked towards consensus.

You keep on saying that the QOL issues are underrepresented. Yet, you have not made an attempt (WP:BOLD) to rectify this imbalance. The same applies to all other areas you are so passionate about. Your only recent contribution is the insertion of two laboratory studies in a section on the clinical safety of grains. Are you actually surprised that I reverted you on that?

If you have a beef with the guidelines, go complain to them. But from a professional perspective the guidelines remain the gold standard until they are updated or overwhelmingly strong evidence displaces the guidelines. I see no overwhelmingly strong evidence. All I see is an enormous flurry of studies, many of which are less than methodologically sound. I think we should take Tim Vickers' clue (below) to restrict ourselves to review articles. JFW | T@lk  22:21, 16 June 2008 (UTC)

Keeping short Then we need to discuss issues before change, I am not going to be BOLD with a 95% chance you will revert the change, If I argue there is clinical evidence that oats are safe for celiacs, then your response should be what is the evidence, provide the papers. Next you critique the evidence. Then we agree what is the best references, the statement is added. Again I added 4 references, 2 on the grains and 2 specifically on oats, it is still apparent you read neither on oats. Here are the clinical references on oat safety, , ,, , , , , , New standards for gluten free foods That should be convincing enough.

At least have the courtesy of crop what was cut and pasting it here for discussion, people make faux-pas. So point to that which is in error.

Lets consider the gold standards: -Oat causes celiac disease - false for >90% of patients. -Clinical atrophy is the only indicator of gluten-sensitive atrophy. -- Even the first studies noted patchy villus atrophy, ignored. Current investigations recommend 8 biopsiess descending away from the duodenum. -- Increased incidences of AID and gastro problems seen in Marsh grade 1 and 2 (sub-clinical) coeliac disease. -- Coeliac disease can be diagnosed with Gene-typing and ATA typing, no great need for biopsy. Standards can be obsolete or wrong. The standard for Oats in GF diet was from 1981, it was apparent that something was amiss by 2003. Through the primary literature we can separate those standards based on facts and those standards based on beleif. While the function of wiki is not to find the truth, it certainly wants to screen out that which is provably not true. This I see as a basic problem. I have seen several sections on oats in Wiki, none of them give any information on the science, or even point to the standard. That is not encyclopedic information, that is simply myth.

I came to a solution, maybe that was the best solution, anyway. I moved the oat controversy off page. What I would like on the main page is and. Pdeitiker (talk) 23:26, 16 June 2008 (UTC)


 * Here's my take:
 * Take Tim Vickers' suggestion and only rely on the conclusions of review articles and meta-analyses. This way you don't fall foul of WP:NOR and WP:SYNTH, and you stand a chance that I will support your edits wholeheartedly.
 * There is presently a professional consensus that oats (i.e. grain products guaranteed not to contain gluten) should be consumed with caution: initially avoid them completely, then reintroduce them while accepting that repeat biopsies or serology may be needed, either routinely or on reappearance of symptoms. This is supported by the two reviews that Tim has kindly identified.
 * AID and "gastro problems" are really vague terms, and the studies that show this are methodologically weak. The same on gluten neuropathies.
 * Professional guidelines demand biopsy, and this is professional consensus until the guidelines are updated or displaced by large prospective studies. Perhaps next year NICE will alter practice in the United Kingdom. Until then we can only do so much in mentioning the diagnosis of coeliac disease sans biopsy.
 * I can't presently support links to oat sensitivity (a neologism) and the oat controversy. With the reviews in our hand we can provide a balanced account of the issues without having to resort to subarticles. JFW | T@lk  23:53, 16 June 2008 (UTC)


 * When it comes to credibility in science 1. Primary literature, 2. Reviews, 3. Books, 4. Newspaper articles about 1, 2 and 3. I look whenever possible at the original data. When it comes to timeliness 1. Primary literature 2. Newspaper 3. reviews 4. books.
 * Pardon me for cutting in here. Why can't we just say what you just said? Provide references (I have those by T. Thompson ready to go). BTW, Thompson states the major reason for taking care is the contamination issue. Just crop it an cite it. Pdeitiker (talk) 01:35, 17 June 2008 (UTC)
 * Yes, but those studies that have followed up celiacs have found a broad smattering of AID that are generally persistent or recurrent on gluten-free diet. QOL issue.Pdeitiker (talk) 01:35, 17 June 2008 (UTC)
 * I agree, but patient perspective, here, again QOL. Low cut insurance providers and 15 minute physicians, they don't want to do biopsies until after the tests come back if that, now-a-days, the will ask the patient if they need a biopsy. I don't know what you have to deal with, but I know what I and a couple of other gluten-sensitive individuals have had to deal with. Patients have to deal with the system as it exists, not as someone in a far off country wishes it might be.Pdeitiker (talk) 01:35, 17 June 2008 (UTC)

I have again disentangled your comments from my bulleted list. Please follow talk page guidelines. I have asked you previously to leave my posts intact.

Credibility in science is not primarily in the primary literature. Please review WP:MEDRS. Reviews have the benefit of having a full survey of the published knowledge on a subject. This is something a primary research study cannot provide. Please also see Tim Vickers' points below and a separate discussion with ImperfectlyInformed. The central place of review studies is not really open to discussion here.

You are free to insert my version of the oat issue with the appropriate reference.

No, AID studies need to be reliable and causally plausible. This is presently lacking. It is not just a QOL issue, it is a treatment issue and a monitoring issue and a screening issue.

I have no idea what relevance "patient perspective" has in this discussion, nor your jibe at 15 minute physicians. If professional guidelines insist on biopsy, then those doctors or organisations deviating from this guideline open themselves up to criticism. Who is "someone in a far off country"? I really don't understand your points here. JFW | T@lk  01:55, 17 June 2008 (UTC)

Comments from ImperfectlyInformed
First, what's wrong with referencing all those PMIDs with one link, Pdeitiker? Anyway, I agree with Tim about using reviews, I just couldn't find any good ones. Thanks for pointing this BMJ one out. Here's what it says on quality of life: My personal feelings on the issue is that recurring problems could be largely attributable to ubiquitous gluten contamination, but I'd like to see what is said about this in the papers. In Europe, for example, maltodextrin is frequently made from wheat while in the US is made from corn (rough source). I'm sure you've mostly heard that. Many people eat packaged foods, or foods with no gluten ingredients, and gluten is frequently in them -- even in very small, allowed amounts. Reference 99 from the BMJ review highlights this issue and claims that many of these symptoms resolve on a completely gluten-free diet -- which probably requires cooking more from scratch than most people do. ImpIn | (t - c) 22:48, 16 June 2008 (UTC)


 * I think it is not helpful to offer long quotes and personal feelings. Please WP:BOLD and improve the article. JFW | T@lk  23:00, 16 June 2008 (UTC)


 * Don't assume that every little roadbump in a coeliacs life is due to gluten.Pdeitiker (talk) 05:43, 17 June 2008 (UTC)

NICE
I think I understand why the BSG has been slow in issuing formal guidelines, given that Prof Ciclitira's guidelines are now 6 years old. The reason is that NICE are working on a clinical guideline for coeliac in adults: http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11880. Looking at the list of stakeholders I am puzzled by the involvement of NHS Direct (since when is coeliac disease a medical emergency?), the National Treatment Agency for Substance Misuse (since when are coeliacs addicts?), and the South Asian Health Foundation (coeliac disease is rather rare in South Asians). I'm sure we'll need to update this article when the guideline appears - it has been scheduled for May 2009. JFW | T@lk  09:26, 15 June 2008 (UTC)

Sorting
It's rather hard to sort the conversation on this page because WP:TALK page conventions aren't being followed: Pdeitiker, would you mind not altering other editors' comments,  signing your edits, and threading your responses under the posts you are responding to? The conversation would be easier to follow if you didn't split up other editors' commentary (see WP:TP and WP:TALK). Sandy Georgia (Talk) 20:23, 16 June 2008 (UTC)

Reviews
This talkpage could be greatly improved if editors relied more heavily on reviews of the topic, rather than referring to personal anecdotes or going through the primary literature themselves and trying to make sense of the large set of conflicting data on this topic. Reviews and meta-analyzes give an expert overview that is much more reliable than trying to integrate several individual studies that each deal with a narrow topic. Tim Vickers (talk) 20:55, 16 June 2008 (UTC)


 * Most papers have succint reviews of the literature in their introduction and discussion sections, which are usually fairly easy to understand. ImpIn | (t - c) 22:48, 16 June 2008 (UTC)


 * Indeed, but if you want to, for example, look at how safe oats are in a gluten-free diet, the best approach is to find a few reviews that examine the topic of how safe oats are in these diets and describe the conclusions of these reviews in the article, rather than selecting papers out of the primary research literature yourself and then synthesizing the conclusions of these papers to form your own view of the field. Expert reviews are the preferred sources for these kind of general articles. Tim Vickers (talk) 16:35, 17 June 2008 (UTC)

Social and religious issues
Since we have this in discussion.
 * 1) This section is redundant with a similarly long section "Religious issues" in Dermatitis herpetiformis. Both articles over-deal with the issue and do not deal with other issues that affect quality of life, including depression, anxiety and anger.
 * 2) This section pertains to all gluten sensitivity, not just celiac disease. If it was moved to gluten sensitivity it would not need to be dealt with twice.
 * 3) This issue is pertinent only to Westerners and those who practice certain religions, at such it can be simplified and shortened.
 * 4) An alternative is to create a new article "Religious issues in gluten sensitivity". This would allow more bandwidth for discussion of other issues.Pdeitiker (talk) 22:37, 16 June 2008 (UTC)


 * 1) Since this article is a featured article, it needs to be comprehensive; what is at Dermatitis herpetiformis isn't relevant here.  Depression, anxiety and anger are given due weight according to reliable reviews.
 * 2) See WP:NOT paper.
 * 3) It's not too long or complex.
 * 4) Shortening of this article isn't necessary; comprehensiveness is the main concern.  Sandy Georgia  (Talk) 22:49, 16 June 2008 (UTC)

I think that mentioning and linking off to a separate article on gluten sensitivity and religious issues, or gluten sensitivity and lifestyle has merit. It's better not to replicate a broad issue like that a bunch of times; it's tiresome for readers to read the same thing over and over, and it is, as Pdeitiker, not directly relevant to coeliac disease, but more directly relevant to coeliac sensitivity. Also, this article should link to gluten sensitivity in the lead, and briefly mention the relationship of the disease to the broader sensitivity affecting people w/o the disease. ImpIn | (t - c) 22:54, 16 June 2008 (UTC)


 * This section is not being split off. Coeliac disease is the most common form of gluten sensitivity, and the other articles can link here for the content in question.
 * I don't think there is any need to link to gluten sensitivity from the lead. Gluten sensitivity is already linked very prominently from the infobox that Phil inserted. Moreover, coeliac disease is a very specific subtype of gluten sensitivity. JFW | T@lk  22:58, 16 June 2008 (UTC)


 * OK. You need to read OWN very carefully, JFW, because you're showing serious symptoms of thinking you own this article. We will decide as a group whether to split off a section -- not you. Sorry. Also, you need to think about improving your tone, because you're not the only temperamental person around. The gluten sensitivity infobox is not all that prominent -- I missed it several times, especially because I tend to click on a section directly from the lead. This article also needs to discuss self-diagnosed "coeliac disease" -- I am self-diagnosed, as are most "coeliacs" that I meet, because once you go off gluten and have great results, it is hard to start eating it again just to have an intestinal biopsy. I have one of the genes for it, a gene for sensitivity, and pretty much all of the symptoms (including positive serology). provides some background, as does . Here is a letter discussing the issue. ImpIn | (t - c) 23:08, 16 June 2008 (UTC)


 * Self-diagnosis could be discussed if reliable, high-quality reviews address the topic; if not, we must take care with WP:UNDUE and not rely on primary sources. II, please avoid inflammatory discussions with other editors, if you have personal issues, please take them to individual editor talk pages, thanks, Sandy Georgia  (Talk) 23:11, 16 June 2008 (UTC)


 * This is a talkpage, and I thought I should make my opinion clear. That isn't WP:OWN and I would obviously yield to articulate and reasonable consensus. I am one of the editors who worked very hard to get this article up to featured status in 2007 so I hope you will forgive me of being somewhat protective of it.
 * I am really not sure if self-diagnosis is to be mentioned. In the end, anyone who self-diagnoses still needs to undergo confirmatory testing by qualified healthcare professionals. JFW | T@lk  23:25, 16 June 2008 (UTC)


 * That is not consistent with policy; we are not restricted to using only reviews of literature. Read WP:OR. The discussion sections of specialized papers are often better than the very brief and general notes in a review of the literature such as the one posted by Tim. Much of the systematic reviewing of specialized literature goes on in later primary papers themselves. I've opened up a discussion on this at the OR talk page, which I will probably open into a RfCpol. ImpIn | (t - c) 23:40, 16 June 2008 (UTC)


 * Yes, please do read WP:OR
 * "Wikipedia articles should rely on reliable, published secondary sources. All interpretive claims, analyses, or synthetic claims about primary sources must be referenced to a secondary source, rather than original analysis of the primary-source material by Wikipedia editors. ... Primary sources that have been published by a reliable source may be used in Wikipedia, but only with care, because it is easy to misuse them."
 * Sandy Georgia (Talk) 14:34, 17 June 2008 (UTC)


 * Sandy, read further. Primary articles may be used if they are clear. Plus, technically speaking, a primary review discussing past literature is a secondary source of information on that literature. The idea that reviews always are more comprehensive is a poor assumption. Look at the review that Tim posted. All it basically does is collect all the reviews on one page. It offers very little analysis. Please reply. ImpIn | (t - c) 10:57, 18 June 2008 (UTC)


 * Policy is that you cannot use a single primary reference to refute a review unless that primary reference is primarily questioning an opinion in the review. Thats what I understand. For example you cannot take something from the discussion of a paper in 1963 to refute an opinion in an 1980 review. OTOH you can use results from a 2008 paper to refute an statement in a review from 1980 if recent paper is specifically directed at the except from the review used.Pdeitiker (talk) 02:01, 17 June 2008 (UTC)


 * Well yeah, don't get ridiculous. Using more recent articles is preferable. When you cite a certain thing, the one which has the most support behind it (papers, or more specifically data) is the one with the most strength. But the idea that the review necessarily improves this is fallacious. The PMJ linked by Tim, as I've pointed out a couple times, offers very little analysis, and this is not uncommon in reviews, especially those with a broad scope. ImpIn | (t - c) 10:57, 18 June 2008 (UTC)


 * There is no such policy. Sandy Georgia  (Talk) 14:34, 17 June 2008 (UTC)


 * There is no such provision in the WP:Verifiability policy. I should know, I helped write the darned thing. Tim Vickers (talk) 16:38, 17 June 2008 (UTC)


 * "All articles must adhere to Wikipedia's neutrality policy, fairly representing all majority and significant-minority viewpoints that have been published by reliable sources, in rough proportion to the prominence of each view." "In general, the most reliable sources are peer-reviewed journals and books published in university presses; university-level textbooks; magazines, journals, and books published by respected publishing houses; and mainstream newspapers. As a rule of thumb, the greater the degree of scrutiny involved in checking facts, analyzing legal issues, and scrutinizing the evidence and arguments of a particular work, the more reliable it is.""For a guideline discussing the reliability of particular types of sources, see Wikipedia:Reliable sources (WP:RS). Because policies take precedence over guidelines, in the case of an inconsistency between this page and that one." If the contradiction isn't obvious, then maybe I live in an alternate universe. This _policy_ says nothing about the precedence of a review over primary literature or restictions on contradicting a review opinion with primary literature. But here in WP:NOR we see "Wikipedia articles should rely on reliable, published secondary sources. All interpretive claims, analyses, or synthetic claims about primary sources must be referenced to a secondary source, rather than original analysis of the primary-source material by Wikipedia editors." and then "Appropriate sourcing can be a complicated issue, and these are general rules. Deciding whether primary or secondary sources are more suitable on any given occasion is a matter of common sense and good editorial judgment, and should be discussed on article talk pages."(ahem)Pdeitiker (talk) 20:45, 17 June 2008 (UTC) Concrete is what we build houses on, not the direction that desires the mind.


 * Yoda confused is he, as policy say, prefer to use secondary sources we do. :) Tim Vickers (talk) 23:34, 17 June 2008 (UTC)


 * Thanks for making that clear. I can understand being protective about it. As far as confirmatory testing, it often does not happen because its uncomfortable and considered by patients (and some doctors) to be largely unnecessary if they feel much better. ***Couple other interesting papers semi-related: physician knowledge of the disease, and prescribing the GF diet without a biopsy. ImpIn | (t - c) 23:40, 16 June 2008 (UTC)


 * Self-diagnosis belongs on the gluten-sensitivity page. Pdeitiker (talk) 23:28, 16 June 2008 (UTC)


 * Self-diagnosis of coeliac disease belonging somewhere that is not not the coeliac disease page? Now I'm confused. What would the point of that be? JFW | T@lk  23:53, 16 June 2008 (UTC)


 * Self-diagnosis belongs nowhere unless it's discussed by reliable secondary sources. Sandy Georgia  (Talk) 14:34, 17 June 2008 (UTC)


 * Non-diagnosis, without ATA & Gene typing or biopsy (preferably looking for IEL or ATA deposits), accompanied by a decrease of symptoms on a gluten-free diet is gluten sensitivity (GS). GS can be divided into gluten-sensitive enteropathy (stage 3 and 4 = coeliac disease). GS can also be an allergy to gluten or wheat. I know of people who firmly believed they had coeliac disease until they were tested, upon testing for food allergies they found they were allergic to wheat. There was a recent study done on gluten exclusion diet with I believe 116 people, the affected consented to gluten-challenge however only half were confirmed as coeliac disease. Studies show that there are about 3 times as many people allergic to wheat as those who are coeliacs. If you need references I can find them for you.Pdeitiker (talk) 01:43, 17 June 2008 (UTC).


 * To respond to ImperfectlyInformed: there is a certain hierarchy in medical sources, and WP:MEDRS accords preference to reviews and meta-analyses pretty much the way professional guidelines prefer that kind of study over isolated reports that have not been replicated.
 * I take your point on a GF diet without biopsy, but this is presently being discouraged as professional guidelines still regard the biopsy is crucial. If people decline to undergo a biopsy they run the risk of treating themselves for nonexisting coeliac disease, however close one gets to a diagnosis with serology and HLA typing. JFW | T@lk  23:53, 16 June 2008 (UTC)


 * I don't disagree with you, but I think the self-diagnosis phenomenon needs to be noted carefully in the diagnosis section. I'll do this shortly after more research. As the letter I cited shows, there is some controversy surrounding the biopsy, and that deserves a sentence or two. After that, I strongly think that gluten sensitivity needs to be noted in the lead where it is harder to miss. And possibly there needs to be a section discussing the relationship between gluten sens. and coeliac disease -- I'm sure there are papers on it. ImpIn | (t - c) 10:57, 18 June 2008 (UTC)

Relative abundance of gluten-sensitive disease
The abundance of coeliac disease. Frequency of coeliac disease in the population is age dependent. See section in Main on tissue transglutaminase and section in talk page on coeliac disease in the elderly. Excluding death as a result of coeliac related conditions the rate appears to climb from about 0.5% to greater than 1.5% over a lifetime. The retrospective studies on biopsies of suspected coeliacs reveal that a small percentage of people, at any one time, are within the Marsh grade 1 and 2 criteria, a process that last up to 5 years. Asymptomatic coeliac disease represents the majority of the coeliac population, the level of diagnosis depends on the country, the Scandinavian countries appear to have the highest rate of diagnosis.

The abundance of allergies. I have seen estimates in the literature that wheat allergy ranges as high as 5% though most place rate of allergy below 3%. Thoroughness of testing is the major deterrent to accurate estimates. The ability to detect wheat allergy depends on the type of testing, and other allergies like ASCA and amylase antibodies that are screened-out. Most wheat allergies are not apparent to the individual, and may be asymptomatic unless they work in an occupation that makes or processes wheat products. In general, the separation of wheat allergies into gluten allergies is not done. Gluten allergies are estimated to be about 1/2 of all wheat allergies. The most severe wheat allergy, to omega-5 gliadin is very rare, but is increasing with the use of aspirin, NSAIDs and low dose aspiring therapy. Most allergies are to the glutenin component of wheat. Mild allergies to gluten can be a factor in IBS, Factor-V Leiden penetrance, clotting abnormalities, HRQOL issues. Wheat is one of the most common allergens found in rheumatoid arthritis. Like coeliac disease there is a large cohort of underdiagnosed allergies. Some of the wheat allergies are secondary to enteropathy. None the less gluten allergies are not a rare fraction of gluten sensitivity. Food allergies to wheat often become apparent only when some underlying stressor is involved. For example excessive exercise after eating, damage to the GI done by aspirin or NSAIDs. A large percentage of NSAID sensitivity, not an allergy to the drug, but the introduction of food allergens into the blood stream. Wheat and crustaceans allergies are two main triggers for anaphylaxis/urticarias that are caused by exercise/aspirin induction.

Idiopathic gluten-sensitivity. gluten-sensitive neuropathies without a clear cause are on the rise. The diagnostic criteria is in question. The proponents of this class of gluten sensitivity place the incidence at about 10 per million, whereas the critics place the incidence below 1 per million individuals. This form of gluten-sensitivity is very rare.

—Preceding unsigned comment added by Pdeitiker  (talk • contribs) 14:14, June 17, 2008


 * Pdeitiker, please sign your talk page entries by entering four tildes ( ~ ) after your posts, and please follow talk page guidelines (WP:TALK, WP:TP) for threading and responding to posts. This talk page is a dog's dinner and hard to parse.  Sandy Georgia  (Talk) 14:29, 17 June 2008 (UTC)
 * SandyGeorgia, please use critiques that make sense "WP:NOT paper" is of little value as a critique, neither is the colloquillism "dog's dinner". Your alteration on the main page "WP:MOS" (Quite large) did not indicate what change you were referring to.Pdeitiker (talk) 16:10, 17 June 2008 (UTC)
 * As a matter of fact, my edit summary specifically referenced the exact paragraph at MoS I was referring to. Sandy Georgia  (Talk) 16:33, 17 June 2008 (UTC)
 * And so what did that have to do with removal of an "s" from factors? That "&nbsp" added was an edit of content made by someone else. The "edit summary" to my edit made no sense to me. Seems to me trivial spelling edits don't need a summary of this type, even so, tell the person on their talk page.Pdeitiker (talk) 17:06, 17 June 2008 (UTC)
 * Edit summaries are not to your edits; the general message on this page is that featured articles must conform to WP:MOS, of which WP:NBSP is one part. Sandy Georgia  (Talk) 14:05, 18 June 2008 (UTC)
 * If it takes 20 minutes to figure out what you changed and why, the lesson you wanted people to learn gets kind-of lost. That is kind of a neat gadget to use, and thanks for posting it. Think about ways of getting your point to work.Pdeitiker (talk) 17:04, 18 June 2008 (UTC)

Changes to diet section
It appears that this change is introducing primary sources based on small samples. (It also uses different citation formatting which will need to be fixed per 2c if the changes remain.) Sandy Georgia  (Talk) 14:05, 18 June 2008 (UTC)


 * I don't really object to the studies in question because the recent clinical reviews don't discuss QOL, and it is still of relevance even to the casual reader. But I think the subject of QOL has now been addressed and no further modifications are needed. I have fixed the citations, which contained some errors. JFW | T@lk  15:05, 18 June 2008 (UTC)


 * Thanks, JFW; hate to see an FA deteriorate, and it's important to stay on top of the little MoS errors before they snowball. Sandy Georgia  (Talk) 15:06, 18 June 2008 (UTC)


 * I must say I've only recent wisened to the intricacies on WP:NBSP and the emdash. JFW | T@lk  17:34, 18 June 2008 (UTC)


 * The review deals withsome of the HRQOL diseases looking at both sides. One point, the reason why study sizes are small because patients are not pooled between multiple study centers. Statistics relies on power and power of the argument can generally be assessed as a function of size of the affected population and the odds ratio. There simply aren't enough study subjects for most associated conditions in any one study center to reach a high degree of significance. The review suggests throwing out case reports and focus on double blined studies, but defends in-promptu 'gluten-free diets' and IV Ig replacement because of the disparity of some conditions. Patients can enter and exit studies at their liberty, biasing the study results. Point, it will take time to trudge through studies to see what associations will hold up.Pdeitiker (talk) 20:27, 18 June 2008 (UTC)


 * I mentioned this on 9 April (see Talk:Coeliac disease/Archive 3). It is not the first study to cast doubt on a large number of possible associations. JFW | T@lk  21:00, 18 June 2008 (UTC)


 * And they should be casting doubt, but in a way that does not discount those studies. See picture on 1st page of review, that is what has been happening and it extends to the genetics also. That is why I don't want to add more on the Main concerning genetics. There is no balanced or objective forum where the actual evidence is available to the mass. If you get tested by a certain lab and you have DQ1 (64% of people have DQ1) they are going to treat the idiopathic gluten sensitivity issue as if 'it' and the DQ associations are settled science. Whereas this page should both expose and take NPOV. In addition, I want to see what the HapMap studies detail on subregional variation, if they find these hypermutable haplotypes are highly localized and correspond with some of the study areas, then I think the design of these studies needs to change and look at family histories and regions. This also applies to diease associated with disease studies. Genetics, diet, environment, life histories all play into these. I asked the question on that last genome-wide paper, are they hitting a locus linked to CD and T1D because T1D brings CD into the study or is it because there is independent linkage to the same locus.Pdeitiker (talk) 01:49, 19 June 2008 (UTC)


 * This has nothing to do with HRQOL. Quality of life is the subjective functioning as a result of illness. Neurological complications are disease entities, not just subjective experiences. JFW | T@lk  21:02, 18 June 2008 (UTC)


 * The review deals largely with methodology of assertion. However there are a couple of QOL issues. 1- When to institute a gluten-free diet when the only finding is anti-gliadin antibodies 2- They talk about prevelance and increase of certain conditions after diagnosis with coeliac disease. 3-The issue of low vitamin and neurological conditions associated. I pointed the review out for the same reason you mention, we can talk about associated diseases but to be neutral, we need to also point out the weaknesses of the studies. In articles dealing with depression, one paper says depression improves on GF diet, and the other paper says depression does not improve. Most of the neurological topics ~ the same.Pdeitiker (talk) 01:49, 19 June 2008 (UTC)


 * I don't think I understand your use of the term QOL. JFW | T@lk  05:59, 19 June 2008 (UTC)


 * Briefly, the new edits made to main/diet section, let us make sure that controversial science is balanced by critiques if those critiques have been made.Pdeitiker (talk) 16:21, 19 June 2008 (UTC)


 * What has that got to do with QOL? The new edits to the diet section reflect current professional standards, which are not displaced by the "critiques" you are citing. They have to do with disease control, not with quality of life as a dedicated indicator. I will not be able to respond sensibly if you cannot clarify why this should be a QOL issue rather than anything else. Again: in medicine QOL is a separate outcome measure, distinct from markers of disease progression or resolution. JFW | T@lk  17:31, 19 June 2008 (UTC)

Prolamin section
(since the changes have been refined to a final form I am refactoring my comments on this material to shorten the material, most of the material cropped is written by myself and so I have good faith I can represent thoughts carefully.)


 * Referring to the iconic review: 1 "Recent advances in coeliac disease".
 * Referring to #1 and discussing the T-cell 'multi'site, "33mer" "'Interestingly, the fact that many gliadin peptides possess bulky hydrophobic amino acids followed by proline blocks the activity of intestinal peptidases such as pepsin and chymotrypsin. Thus gluten peptides able to stimulate T cells (such as a recently described 33mer sequence) are resistant to degradation by all gastric, pancreatic, and intestinal brush border membrane proteases in the human intestine.'1"
 * Referring to #2 and discussing the innate "19mer" "'Several recent reports have suggested that one of the first events in coeliac disease pathogenesis may be a direct effect of certain wheat peptides, distinct from those recognised by T cells, on the intestinal epithelium. One such peptide, wheat A-gliadin p31-43 (LGQQQPFPPQQPY) or p31-49 induces changes associated with coeliac disease on intraduodenal administration, and in vitro in biopsy based studies.'1"
 * Referring to #3 and discussing the factors involved in increased permeability and Zonulin release. "'Direct effects of gliadin on enterocytes may also increase intestinal permeability through release of zonulin and effects on intracellular tight junctions.'1"Pdeitiker (talk) 19:21, 19 June 2008 (UTC)

Use of the word gluten
Concerning a recent edit: " Gluten-free products are usually more expensive and harder to find than common gluten-containing foods." This somewhat reflects modern standards of cooking in which starting ingredients or whole meals are prepared and packaged. The basic starting ingredients for most gluten-free products are cheap. Apples, oranges, and dried beans and corn are always gluten free. The QOL issue is the added time coeliacs who want a healthy lifestyle on a modest budget will spend preparing food. 2nd issue Gluten-free is defined, gluten-containing has 3 different possible definitions.Pdeitiker (talk) 20:08, 20 June 2008 (UTC)


 * You are again using the term QOL in a totally unrelated context. Could you please explain what you mean when you refer to this elusive concept? JFW | T@lk  22:39, 21 June 2008 (UTC)


 * I did not use HRQOL in this instance. I think the section can be cleaned up and a little more objective. One can consider that a Lacodan Mayan has no loss of QOL or greater expense on a GF diet for food given they are not westernized and there are no indigeonous cultivars of Triticeae. Whereas those children in refuge camps that suddenly show up with CD after getting international food handouts, of course the alternative is also not pleasant. To stay on the point, QOL in this instance is this instance is a matter of convenience, for example in most areas of the US gluten free choices for dining out are limited, and require substantial education and support, some people, and I have heard this from a number, just don't go out, another QOL issue. These are not necessarily more expensive. However trying to substitute old wheat-containing diet with an exactly comparable GF diet is expensive and difficult, and, for instance, there is no comparable substitute for bread. There are other breads, for example corn tortillas, and they are in fact cheaper and healthier than most breads, the sacrifice is in the quality of taste one expects, so that is another QOL issue. Many articles have discussed this issue, and I will reference these tomorrow, adults in particular are accustomed to a certain food culture, and a GF-diet and dining-out issues can result in depression and other QOL issues.Pdeitiker (talk) 03:10, 23 June 2008 (UTC)


 * Remember that Featured articles need to have a SUMMARY style. Lots of stuff on a gluten-free diet and lifestyle should go in the gluten-free diet page, and if necessary a gluten-free diet and lifestyle page. ImpIn | (t - c) 03:58, 23 June 2008 (UTC)


 * The gluten-free page is a mess.Pdeitiker (talk) 17:34, 23 June 2008 (UTC)


 * Before anyone tries rhapsodizing about the "superior" benefits of GF substitutes, keep in mind that not only the taste quality is not as good, but they are difficult to use - corn tortillas will break apart unless they are heated to high temperatures. Try eating a sandwich when the bread literally unravels.  The same is true for all substitutes.  As for eating out, GF sufferers are not hermits - they are part of families and other social groups.  Try being the one who cannot have anything while everyone else has a meal.  Anyone who thinks this is a good thing is as insensitive as the physician who believes that celiacs should continue to ingest gluten because it would be good at preventing heart disease.  Months ago, I posted a question on the oats in the discussion section, but then it was removed without any explanation.  As someone whose gluten intolerance includes oats, I find that unacceptable and unscholarly.  I thought the idea of the discussion section is to maintain a history of the discussion of issues, not as an opportunity for removing unfavorable ideas.maclilus (talk) 15:19, 17 December 2008 (UTC)

Adding a mention of gluten sensitivity to the lead
SandyGeorgia just reverted my addition to the lead (diff). LEAD states that the lead "should establish context, summarize the most important points, explain why the subject is interesting or notable, and briefly describe its notable controversies". Gluten sensitivity is important context. Let's hear what other people have to say. It seems SandyGeorgia opposes this addition. I want to hear JFD, TimVickers' and Ptdeikers' position -- as well as anyone else. Please concisely reply. If we can't agree to put it in, I'll put up a RFC. That article has too much important information, and it is too easy to miss currently in the template. ImpIn | (t - c) 04:08, 23 June 2008 (UTC)


 * None of my major sources for this article refers to the concept "gluten sensitivity". What is the reason that you think it should be given this level of prominence? I think the onus is on you to demonstrate this, not vice versa.
 * I am a bit concerned about your choice of words above: "If we can't agree to put it in." Does that mean you will yield to consensus, or will you fight it all the way? Because I can predict the responses from Tim and Phil (and Sandy for that matter). JFW | T@lk  05:29, 23 June 2008 (UTC)


 * Pubmed for "gluten sensitivity"[All Fields] gives 190 citations. This is piddly compared to 12413 for "celiac disease". Most of the citations yielded by "gluten sensitivity" are about GSE anyway and not about this elusive concept of "hmm my patient is ill and has anti-gliadin antibodies - interesting... never mind that they don't respond to a diet".JFW | T@lk  05:48, 23 June 2008 (UTC)


 * I think is an example of the protagonists of this concept, which is by no means accepted in the coeliac disease research community and cannot possibly be discussed in the lead with such a degree of prominence. JFW |  T@lk  05:48, 23 June 2008 (UTC)


 * Well put, but also the third party testing lab that finds idiopathic disease under every DQ1 type, never mind that excluding all DQ2 and DQ8s from the populatin DQ1 represents about 90% of what is left.Pdeitiker (talk) 06:23, 23 June 2008 (UTC)


 * I was practically kicked into creating that page, it was by no means a great joy to create. Let me put it like this, biochemist like myself like to have pretty categories to place things into. Gluten sensitivity is not one of those categories. Although the page has evolved with new information, and it serves auxiliary function. Coeliac disease has a set of diagnostic responses that are not shared by the other two diseases (if you can count the GS idiopathic neuropathies as a disease). The membrane permeability issues appears to be independent between EIA and CD (although many CD have wheat induced urticaria and aspirin sensitivities). Let us wait on the issue of creating a universal umbrella for coeliac disease in gluten sensitivity when many papers still treat GS as suspect GSE without a diagnosis (such as in newly diagnosed derm. herp.). The difference, is that a person who finds the GS page first may enter as a result of some third party testing lab that finds GS under tea leaves, whereas if they enter CD they might have been told they have gluten sensitivity as a result of dermatitis herpetiformis. Probably my opinion is going to change with more work on innate immunity (and a review that makes everyone happy).
 * By the way, I would classify gluten sensitivity outside of coeliac disease a notable controversy. No-one contests that CD exists, but there is a contest over idiopathic sensitivity and whether some aspects of these allergies are allergies or more deeply rooted intolerances. In terms of linking to that page, let me just say, the title is designed to pickup direct from the internet as to route people toward the CD page, not away. JFW added the linking box to the Main.Pdeitiker (talk) 06:14, 23 June 2008 (UTC)
 * I would like to see more linkout to the oat controversy on that page. I think I have done a really good job of defining the controversy. :^).Pdeitiker (talk) 06:14, 23 June 2008 (UTC)


 * So, Phil, what is your opinion on linking gluten sensitivity from the lead? This discussion is not about DQ1 and third party testing. You seem to suggest that the page by that name is simply an overflow because you have been stopped from using the coeliac disease page to put all that content. JFW | T@lk  06:31, 23 June 2008 (UTC)


 * At this point in time it is unnecessary. The issue of adding to this page needs a developed process of creation and discussion. That process may also need background, as the genetics section did. All of the new issues are increasingly complicated.Pdeitiker (talk) 14:26, 23 June 2008 (UTC)

Since it is such a big deal, I'll drop it. In the future it may have to be added. Gluten sensitivity is mentioned in this (pdf) overview of current research from the Celiac Disease Foundation (in addition, the intestinal biopsy debate is mentioned). Worth looking at. ImpIn | (t - c) 06:50, 23 June 2008 (UTC)


 * Fasano says that the phenomenon of "gluten sensitivity sans coeliac" is awaiting confirmation. That is actually perfect evidence to support my skepticism. Thanks. JFW | T@lk  11:36, 23 June 2008 (UTC)


 * Right, but we can add information that underlies the changing concept of prolamins without embracing a holo-concept of gluten sensitivity. Gluten-sensitivity is like 'slims' disease or god, it exists because people believe 'it exists' (in fact that is the Mosaic definition of god), in that light gluten-sensitivity will likely grow in acceptance. OTOH, people are at a richly designed site, this page. Some these people are self-diagnosed which really means they are gluten-sensitive. As I told ImpInf,  if he wants to create a self-diagnosis section he can add it to the GS page and we can see what becomes of it. I was looking for a paper but I could not find it, it claimed something of 120 people who refused typing but were placed on a GF diet because of symptoms after eating wheat about half on gluten challenge had GSE the other half? Why they did not test for other sensitivity, wheat allergy?Pdeitiker (talk) 14:27, 23 June 2008 (UTC)
 * That is the problem in the way people think, you can't have a result unless biopsy, fine, but then if the result is negative what are you as a researcher going to do. Another paper showed that post-treatment diarrhoea in CD ussually has an explanation that physicians simply do not investigate the symptoms. I know 2 people who thought they might be CD one had the gene the other did not both ended up having gluten allergy, one had a very severe allergy and she had to pay for the testing out of pocket. If the physicians did proper testing 'gluten sensitivity' would not exist.Pdeitiker (talk) 14:26, 23 June 2008 (UTC)

Reliable sources
Please confine edits to reliable sources; Celiac.com is not an adequate source for any article, and certainly not for a featured article.   I will make the MoS corrections, but since this text is not based on a reliable source, it will still need to be corrected. Please take care not to cause deterioration to a featured article but introducing non-reliable sources and MoS errors. Thanks, Sandy Georgia  (Talk) 04:55, 23 June 2008 (UTC)


 * Since it was used as a source already, I assumed that it was fine (ref 72). I disagree with you that it's unreliable for these claims -- these are uncontroversial, non-scientific statements. Should I post a notice to RS/N? Do we have to go to dispute resolution for this as well? ImpIn | (t - c) 05:02, 23 June 2008 (UTC)
 * That type of text should be sourceable to a reliable source. Sandy Georgia  (Talk) 05:10, 23 June 2008 (UTC) (Perhaps you can see the difference between citing text relating to an Italian organization and text related to FDA regulation in the USA in terms of the sources expected ??)  Sandy Georgia  (Talk) 05:13, 23 June 2008 (UTC)


 * You write that as if you expect me to see a difference. :p I don't. Both are standard reporting -- can you please elaborate on the difference? If we can trust Celiac.com (run by a US citizen) to report on some Italian organization correctly, why should we not trust them to report on the standards in the US correctly? If you want to source to the FDA so badly, here is the most recent link. How about the other places where Celiac.com is used? And do I read you correctly in implying that you are OK with ref 72? ImpIn | (t - c) 05:25, 23 June 2008 (UTC)


 * Sandy, if there is a problem with the regulation of the concept "gluten free", then FDA and Celiac.com sources may be notable. Clearly, this label is not as strictly regulated as one would wish. To compare, in the USA a product can only be labeled "kosher" if it has been thus certified by a rabbinic authority. Working in the UK I am not very familiar with this debate, but it seems to me that patient organisations are pressurising the FDA to tighten up on gluten free labelling.
 * Obviously, if this can be sourced to more reliable print sources, or to peer-reviewed journals, we'd all be happier. JFW | T@lk  05:33, 23 June 2008 (UTC)


 * On reflection, I notice that celiac.com is nothing more than a glorified blog. Could there be better sources on celiac.ORG, the site of the Celiac Disease Foundation? JFW | T@lk  06:08, 23 June 2008 (UTC)


 * It's a bit much to say that it is a glorified blog -- its a clearinghouse for information on CD, including a store for gluten-free food. The claims that celiac.com are making are really uncontroversial: 1) that the GF label is not regulated in the US (true -- this can be replaced by FDA link), and 2) that most "gluten-free" products contain traces of gluten -- accepted in the Codex standards, widely known, obvious. Partly I linked to celiac.com for its decent explanation of how the standards work, but if we can find a better, recent overview, that would be great. The literature that I've glanced at seems to skip over a discussion on this. [unsigned message]


 * I think I have been quite explicit in what the standards (at least where to find them) are under the oat controversy. We actually do not know how much gluten is in gluten free products, 1. The new tests are only now being widely used 2. There is no quantitation below 10 PPM. I have never had any problem with a product stated as gluten-free, I have had problems with products which do not state wheat on the label, but switch between different flours for 'whatever' reason. The major offender was not a US company. The US is currently waiting for the Codex revision for the very simple reason - international conformity. Supposes BRM wants to sell gluten-free pancake mix in brazil if there are two national standards, his products could be blocked at the port.Pdeitiker (talk) 14:01, 23 June 2008 (UTC)
 * [BTW, if you want to point to a failure in the US, the FDA tolerates labeling of oats which IMHO gives a clear nod to contamination issues]


 * It has recipes mixed in with news and opinion by various people. Information on the page doesn't seem to reflect the official policy of any organisation. There must be better sources. JFW | T@lk  11:39, 23 June 2008 (UTC)

Idiopathic Gluten Sensitivity
Otherwise known in the literature as gluten-sensitive idiopathic neuropathy is defined as a collection of conditions (e.g. ataxia, peripheral neuropathy, epilepsy) that fail to meet known criteria and that have higher than expected frequencies of anti-gliadin antibodies(AGA). The questions involved in this criteria are not simple and the answers to date have not been concise. This situation became known to me not by reading the literature, but from celiacs themselves claiming that they were diagnosed by this or that lab. Therefore since the commoner is aware of the disease I felt it was worthy of a wiki, same as Cabal is worthy of a wiki.Pdeitiker (talk) 17:17, 23 June 2008 (UTC)

Here are the negative points.

1. The authors claim there is an association with DQ1. In fact the most obvious association was with DQ2 in both of their studies. DQ1 did not appear to reach significant levels when DQ2 was removed. They themselves have done no statistical analysis, and they should not have reported the find. DQ1 consists of DQ5 and DQ6, DQ5 consists of 3 not-rare haplotypes and DQ6 consists of 6. In my studies of antigen presentation different DQcis haplotypes behave differently, some the similarily (like DQ6.2 and DQ6.4, ) in other studies those haplotypes behave differently. I do not expect there can be a common theme with all DQ1 haplotypes. Unfortunately this 'find' and AGA+ (even if slight) is the hook that is given to people by some testing labs as they get a piece of paper telling them they are gluten sensitive.Pdeitiker (talk) 17:17, 23 June 2008 (UTC) 2. The authors claim there is significant increase of AGA. The AGA test is notorious for variability in different researchers hands, some quote AGA binding in controls as low as 4% and others report binding as high as 20%. The authors do not disclose the titer of the AGA found in patients and they use historic controls (not responses in their own hands), in coeliac disease the titers can be quite high.Pdeitiker (talk) 17:17, 23 June 2008 (UTC)

3. A recent review of biopsy technique reveals that frequent misdiagnosis of coeliac disease is the result of a physicians myth, that all celiac disease appears first in the duodenal area. Early stage 3 can demonstrate patchy villous atrophy, the most potent gliadin motifs need enzymatic processing which may present the most active sites distal to the doudenum. This study recommends six biopsies proceeding down from the duodenum. Other studies show an increase of secondary diseases as biopsies become IEL enriched, indicating even low levels of inflammation put the patient at risk. I don't see that these IGS studies sought to exhaustively remove the GSE component.Pdeitiker (talk) 17:17, 23 June 2008 (UTC)

4. They did no allergy testing on these individuals to see if they had hidden allergies or intolerances. Gluten allergies have been noted with increase in two subclasses of IgG, and with the finding that omega-gliadin entering blood stream via a GS mechanism, there is a very good potential of developing AGA. Allergic disease with lower GI phenomena can be associated with neurological problems, fibormyalgia, penetrance of factor V leiden, blood clotting abnormalities, etc. In individuals who may be taking aspirin or NSAIDS in excess of what they are tolerant it is likely that some gluten is becoming systemic, they might be having both allergic responses or sensitivities. In the case of omega-5 gliadin, allergic reactions were only revealed after the protein was purified and digested, therefore rigorous allergy testing for wheat is frequently avoided, in this instance you cannot call it idiopathic unless allergies were part of the testing. To emphasize the point, high levels of AGA in the blood may represent other diseases related to the intestinal activity.Pdeitiker (talk) 17:17, 23 June 2008 (UTC)

Conclusion. The increased finding of DQ2, the questions about how they eliminated GSE from consideration lead me to believe that with very careful screening that some of the patients would be eliminated as a result of GSE or even CD. This would have lowered the cohort (%) of AGA+ individuals. Others may have had allergies and the inflammatory responses associated with those allergies may have caused neuropathies. If the authors are proporting (hyping) IGS then is it in their interest to find all GSE? What I need to see is a finite definition boundary between IGS, GSE and Allergy such that the genetic testing and serological testing has some meaning. As long as they cannot do that, then no-one should accept this phenomena as settled science.Pdeitiker (talk) 17:17, 23 June 2008 (UTC)

Positive points: Some of the clinics in the US are seeing an association between dementia and gluten-sensitivity. GSE in elderly people may not meet the criteria seen in younger people, they may present disease with lower AGA titers and lower ATA titers than younger people. A recent study presented here shows an increase in disease in the 60 to 70 old cohort as cryptic disease, often presenting some symptoms. I am not stating these findings as facts, just that gluten-sensitivity in the elderly can present with confusing symptoms that may represent GSE. Proof of gluten-sensitivity needs to be made from the basic science upward to clinical observations including some testing methodology other than AGA and DQ typing. Some of that new information is coming forward but the information is _still_ known-disease specific, not idiopathic. That means the information has not been tested outside the known context of GSE and wheat allergy. One can easily see from this why I had reservations about creating a gluten-sensitivity page and GS idiopathic neuropathy page. Pdeitiker (talk) 17:17, 23 June 2008 (UTC) [Lifelong member of the TIN Cabal]


 * What are you trying to say, Phil? Most of what you are writing are personal observations. Why the reference to Cabal? JFW | T@lk  17:35, 23 June 2008 (UTC)


 * The cabal does not exist, and yet there is a wiki for it, quite elaborate, that explains that it does not exist and makes fun of people who mention it. TIN Cabal = There Is No Cabal.Pdeitiker (talk) 20:40, 23 June 2008 (UTC)
 * "What I need to see is a finite definition boundary between IGS, GSE and Allergy such that the genetic testing and serological testing has some meaning. As long as they cannot do that, then no-one should accept this phenomena as settled science.me, herePdeitiker (talk) 20:40, 23 June 2008 (UTC)"


 * I know there is no Cabal. We discussed that extensively at our last meeting. Fnord.
 * Given that you agree on the significant problems with IGS/GSE/Allergy, can we agree that we need to be very careful about presenting this information with anything approaching certainty? JFW | T@lk  21:09, 23 June 2008 (UTC)

A review on innate responses in coeliac disease
Recent evidence shows that a 25 mer that contains an innate 13mer in alpha-9 and other gliadins can turn on the immune response in coeliacs but not normal individuals. The addition of immunodominant peptides is thus primed for destruction.Pdeitiker (talk) 13:48, 24 June 2008 (UTC)

Diagnosis controversy, casein sensitivity, and budesonide as experimental

 * The neuroceliac paper (doi::10.1136/jnnp.2007.139717 I believe?) which JFW likes says that the accuracy (i.e. specificity?) of AGA IgA is 90%-98%. DOI is not working currently for some reason.


 * It is not clear what the difference is between the two AGA IgA's in the Blood tests section, aside from the different


 * If I'm reading this right, 50% of the coeliacs sampled in this 2007 study reacted to casein similar to the way they reacted to gluten?


 * The diagnosis controversy references: Fasano: Can we eliminate the intestinal biopsy?, prescribing the GF diet without a biopsy, 1/3 self-diagnosed may not have the disease, letter, and a biopsy is not always necessary for diagnosis.ImpIn | (t - c) 06:44, 28 June 2008 (UTC)


 * Can we add this budenoside study to the list of experimental treatments? Could be very valuable to physicians with refractory patients. ImpIn | (t - c) 06:44, 28 June 2008 (UTC)


 * (DOI indeed broken) takes its information on AGA from . We already have a source for the relative sensitivities and specificities of coeliac serology.
 * The IgA AGA seems to be an error that has gone uncorrected for some time. I discovered that the source is rubbish and that we should read the table only if we can populate it with data from HillNIH.
 * Casein: just wait until it is reviewed.
 * Self-diagnosis and diagnosis without biopsy: how about you try to write this into the article and we'll see if it survives WP:BRD.
 * Budesonide: just wait until it is reviewed. We are not a textbook for physicians, we are a general purpose encyclopedia. JFW | T@lk  07:30, 29 June 2008 (UTC)


 * There is another study out that claims antibodies to select gliadin peptides is far more accurate than AGA, unfortunately it is not in wide use, and it has not undergone other review.PB666 yap 17:46, 29 June 2008 (UTC)


 * Most biopsy diagnosed coeliacs are lactose intolerant, casein 'allergy' is a very common find, in fact casien intolerance in children is suspected as the result of early use of cows milk in the time period when children go through early gastrointestinal diseases, such as rotavirus. This is a suspected cause of coeliacs also. Casien has several transglutaminase reactive sites, GI damage caused by coeliacs can expose casien to tTG, same as gluten, causing increased 'allergies'. Because these proteins can enter the lamina propria and points beyond they can develope IgA and IgG, not just IgE seen with typical allergies. PB666 yap 17:46, 29 June 2008 (UTC)


 * 50% of coeliacs are intolerant to at least one other food, and most have multiple food sensitivities. The very nature of tTG crosslinking gliadin to other proteins is a potent explanation for both extended allergies to food, as well as autoantibody formation in autoimmune disease. The problem, that what I am trying to study, is why autoimmune disease does not revert when gliadin is removed from the system. Some coeliacs have claimed some relief from inflammatory diseases when sensitizing foods are detected and removed from the diet, however these secondary immune conditions remain. A complicating factor in assessing the autoimmune link is that GSE causes maladsorption, including of treatment therapies. So that improvement in treatability on a GF diet is expected for independent reasons.


 * I am going to add a small section on this to gluten sensitivity, this is most important on that page. " 1/3 self-diagnosed may not have the disease", but they likely have some other disease. As the case was made treated coeliacs often continued to have diarrhoea and other problems. Irritable bowel is sensitive to both inflammatory chemicals in the diet (such as arachidonic acid) and food allergens. Inflammatory bowel disease (e.g. crohns and microscopic) is linked to ASCA, ASCA may be caused by yeast mannins in foods and drink (bread having the highest content). 60% of coeliacs have ASCA by one study, but ASCA are not limited to Coeliacs, people with low lectin binding proteins may also have ASCA. Cessation of wheat consumption may have positive benefits to the patient, and because really good allergy tests are very expensive, most PCPs are reluctant to advise on these. Cessation of wheat consumption can: remove gluten allergens, remove non-gluten allergens, remove fungal amylase (a potent allergen), remove yeast-mannins, remove a high starch source, remove alot of junk food from the diet. Others do not accept the use of lymphocyte activation and stimulation (LEAP) tests that simply look to see if a persons lymph cells respond when presented with a chemical or food. I know some who swear that the results of these tests have change their lives. Wheat sensitivity is a common find in people who have negative biopsy results. In addition to wheat, dairy, legumes, bran from other grains, fructose in fructose intolerant individuals, etc can cause the over growth of bacteria and fungi in the ileum and ascending colon, this can cause the production of ASCA and bacterial toxins that inflame the sensitive bowel. So . . . . .The whole gluten-sensitivity thing has become a turf battle. It ranges from old school MDs who do not believe sensitivity can be anything beyond a positive biopsy, to those that find gluten-sensitivity under every DQ type. Symptoms after coeliac, or people who a wheat sensitive after negative biopsy need to be followed up to find the cause, in most cases this is currently not being done and can be coupled with the 85% misdiagnosis rate. With gluten sensitivity, information leads the only effective treatment (that's a hint, BTW).PB666 yap 17:46, 29 June 2008 (UTC)


 * Refractory disease is a multifaceted disease. 1. Patients who have too much Triticeae gluten in their diet 2. Patients that heal on a delayed time frame, 3. Patients with RCD1 and there are affective treatments, and 4. Patients with RCD2 that must be treated very effectively. Some believe that bone marrow transplant before full blown EATL occurs may be the best treatment. The 5 years survival rate for RCD2 is very low. 3 and 4 can be devastating complications.PB666 yap 17:46, 29 June 2008 (UTC)
 * My opinion is that the RCD section needs some fleshing out, but that is not my cause. I think the strong genetic association with DQ2 homozygotes needs to be added. JFW is always talking about the need for biopsy, but RCD2 is a really good reason why late onset disease needs high resolution HLA-DQ typing. DQ2.5/DQ2.x patients are more at risk for severe destruction and other complications. People (and their physicians) who are DQ2hzs diagnosed after 40ya should be aware of the greatly increased risk for life-threatening disease.PB666 yap 17:46, 29 June 2008 (UTC)


 * Phil, I don't think ImperfectlyInformed was asking you for your opinion on the subjects he listed, especially not the verbose response above. He wanted to hear our opinion on including those subjects into the article. By the way, who on earth uses bone marrow transplant before treating EATL? And why are you telling us? JFW | T@lk  19:23, 29 June 2008 (UTC)


 * 1. I was correcting what I though were some incorrect assumptions. 1. Dairy intolerance is common, but what about allergy/inolerance to the other six allergens. Eggs, Shellfish, Fish, Treenuts, Peanuts, and Soy. Why single out casein intolerance. Unless there is a specific good reason for having casein specifically treated on the page, I am against it.PB666 yap 19:57, 29 June 2008 (UTC)
 * Note: higher incidence is expected in early onset disease given it is a major allergen and that it is consumed with the onset of early disease.PB666 yap 19:57, 29 June 2008 (UTC)
 * 2. Martians ? I know, its the little green pygmies that dance around the north pole? I will strike the statement on bone marrow. Clinicians have suggested alot of things, but to point it does not belong here. That discussion aside, the section of RCD is in need of an expansion, but my focus is on prolamins right now and will remain so until the improvements are complete. OK, that aside, let me play a second.


 * "the only possibility of preventing EATL development in RCD being autologous bone marrow transplantation.undefined"


 * so the answer would be: Meijer JW, Mulder CJ, Goerres MG, Boot H, and Schweizer JJ, Dept. of Pathology, Rijnstate Hospital, Arnhem, The Netherlands (aren't you in the netherlands? don't take me too seriously). Fun aside - that strategy would only work if the physician is surveying for refractory disease, and on what basis? There in lies the importance of the age of onset and HR HLA-DQ typing, exactly to my point, a summary of age-of-onset risks and DQ-type risk belong in the main. De novo GS-EATL has no effective preventive treatment since the patient is diagnosed with CD after EATL.PB666 yap 19:57, 29 June 2008 (UTC)


 * 3. Is there any possible way I can get the information for the AGA table so that I can fix it, what are we going to do about this situation, if nothing, we need to scrap it. Its been pointed out by at least 3 different people, it detracts from the clarity of the page.PB666 yap 19:57, 29 June 2008 (UTC)

NIH concensus-Hill
I am not in the Netherlands. The AGA table should be based on the HillNIH reference which is already linked for other reasons. JFW | T@lk  21:43, 29 June 2008 (UTC)


 * OK, I am looking at the PDF. What I see are ranges in percent of various studies that are taken from the primary literature. This information is not suitable in this form for the main. One has to be careful in translating the table. Some studies use human recombinant tTG and others use guinea pig tTG, so the percents are not comparable. One for AGA found 57%, which is an extreme outlyer for other studies.PB666 yap 15:29, 3 July 2008 (UTC)
 * On the Issue of the IgA-less phenotype. IgA-less allele is enriched in all people who have DR3-DQ2.5. Its apparent highest frequency is in North Africa, where western European A1-B8-DR3-DQ2.5 most likely originated. Since there are many homozygotes of DQ2.5 the risk of the IgA-less phenotype is much higher, simply as piggy back phenomena. DQ phenotyping prior to assay is the best way of predicting IgA-less phenotype prior to serotyping.PB666 yap 15:29, 3 July 2008 (UTC)
 * The NIH concensus is great, but I think it is wiser to base the table on secure primary reference, if one can agree on the best techniques and note the technique either in reference or at the bottom of the table. I don't have perfect memory, but some of the testing that was published was below par. In regard to idiopathic disease, there was bantor about some labs getting 4% false positive rate, while others got 15% false negative rate with AGA, and the folks who got 4% rates claiming that others were using improper technique. The problem is that AGA is a mixed antisera, one researcher who used specific antibodies against a-2 gliadin showed specificity and sensitivity comparable to tTG. Inclusion of AGA values is troubled.PB666 yap 15:29, 3 July 2008 (UTC)

Misunderstanding of secondary in the context of primary studies and reviews
I've seen persistent misunderstanding of the "secondary" by TimVickers and SandyGeorgia, which they seem unwilling to discuss. This misunderstanding is essentially called "policy" on WP:MEDRS. A primary study reviews prior studies frequently, making it secondary. They also don't seem to differentiate between a systematic review and a "review". The former limits bias by looking at all papers; the latter can be so broad that it essentially just surveys a topic and misses many papers. The review pointed out by Tim was the latter of these. I don't think that broad reviews are much better per se than the discussion sections of primary papers -- although I'm open to discussing at WT:NOR, where I have an open RfC on this issue. I think the importance of date is underestimated. I've also noted this just now at WP:MEDRS. ImpIn | (t - c) 06:44, 28 June 2008 (UTC)


 * This is really something you ought to be discussing on WT:MEDRS, but on the whole we are expected to find the best source available. If there is a Cochrane Collaboration review available, then other reviews (often with potential COIs and unsourced expert opinion) become relatively unreliable. We are allowed to use editorial judgement, you know? JFW | T@lk  07:30, 29 June 2008 (UTC)


 * yep.PB666 yap 18:08, 29 June 2008 (UTC)

Need for diagnostics
On June 16 2008 JFW said: "T@lk 23:53, 16 June 2008 (UTC)"

Let me play the devil's advocate here for a moment (note I agree with the comment). The gluten-free diet is a lifestyle choice some choose to make, so I have no big problem with that diet, a gluten-less diet would serve many people well. In addition there can be sensitivities to wheat that are not manifested by coeliac disease, such as cryptic allergies, or some of the peptides in wheat could be damaging the GI with other medications (aspirin or NSAIDS) and because they lack the gene will never develope celiac disease. In fact a recent study of people who had treated CD when exposed to wheat, all reverted to CD except one individual who lack the genetic predisposition. For what specific reasons should one have a diagnosis to discriminate 'perception of gluten sensitivity' into various causes.PB666 yap 16:27, 29 June 2008 (UTC)


 * Back to first principles: do we have sources reliable enough to introduce this into the coeliac disease article? Otherwise this thread is going nowhere. JFW | T@lk  19:27, 29 June 2008 (UTC)


 * Don't take the question the wrong way. For the sake of the question, contemporary primary or secondary sources will do, what are the specific recommendations at present for the diagnosis of treated or untreated undiagnosed gluten sensitivity. Previously you mentioned Whipple's disease, is this the only reason or is there a cohesive critique.PB666 yap 20:06, 29 June 2008 (UTC)
 * Note: this is in regard to the question I-I asked and also toward improving NPOV in gluten sensitivity.PB666 yap 20:11, 29 June 2008 (UTC)


 * Like the article says: normally gluten sensitivity would require serology followed by biopsy. JFW | T@lk  21:43, 29 June 2008 (UTC)


 * Can you be specific, which publication? PB666 yap
 * I found it -
 * 21. Hopper A, Cross S, Hurlstone D, McAlindon M, Lobo A, Hadjivassiliou M, Sloan M, Dixon S, Sanders D (2007). "Pre-endoscopy serological testing for coeliac disease: evaluation of a clinical decision tool". BMJ 334: 729. doi:10.1136/bmj.39133.668681.BE. . Full text at PMC: 1847864PB666 yap

2007 review from NEJM
Here is the review. I think it is freely available. Not sure if there's anything that needs to be filled out, but a freely available recent review from a "high-quality" journal might be nice to include. II | (t - c) 03:42, 16 July 2008 (UTC)


 * The Gut article used presently to support most the article is free. The NEJM review you pointed out isn't. Neither is Peter Green and Jabri's Lancet review from 2003 . The only other recent review in a core journal is, incidentally also by Peter Green and associates, from 2005.JFW | T@lk  06:14, 16 July 2008 (UTC)
 * Let's get the pointers right folks, that article is about C-myc from 1992.PB666 yap 20:10, 16 July 2008 (UTC)


 * Sorry, it was . WikEd is playing up & sometimes loses my digits. JFW | T@lk  08:36, 18 July 2008 (UTC)

I think we need to get away from setting up artificial hurdles for editors to jump over. I don't think the idea of the guidelines was to lock peoples feet in concrete on featured articles. If the NEJM adds information that is deficient or biased in the Gut review then it should be appropriate to introduce. For one we don't want to look as if we are a web copy of Van Heel and West and secondarily I noticed some very weak areas in Van Heel and West. They may represent a certain point of veiw, and minority and other major points of view are allowed on wikipedia. Now that I have finished the prolamin section I will look at it. Tomorrow. Lets try to remain objective and open minded. PB666 yap 03:35, 21 July 2008 (UTC)


 * You are free to introduce points from other reviews if necessary. Which ones did you have in mind? I totally agree that we should not restrict ourselves to one review. I have problems, however, with allowing primary research, as has been pointed out numerous times. JFW | T@lk  10:07, 21 July 2008 (UTC)

Proposed changes to Prolamin section
This is a proposal for the change in the prolamin section along with references.


 * -PB666 yap 17:26, 21 July 2008 (UTC)

Back ground info on DQ2.5 and DQ2.2
At the risk of dragging this aspect out one step further. I had been hunting for a particular paper and I finally found it, so that I can support the case. The first is a genetic aspect. This study comes from the Netherlands in this area of Europe DQ2.5 negative DQ8 negative patients are very low. Here are the phenotypes DQ2.5 = DQA1*0501:DQB1*0201, DQ2.2 = DQA1*0201:DQB1*0202, DQ7.5 = DQA1*0505:DQB1*0301, DQ8.1 = DQA1*0301:DQB1*0302 This trend is seen in one other study, except homozygotes are lower in frequency. The point I want to make about this if DQ2 (beta chain) and DQ alpha 5 are contributing equally, then the percentage should be about the same however DQ2.5/DQ2.2 are substantially higher (p=0.022). The finding agrees with. We know the alpha chains of *0505 and *0501 are identical. One explanation is that DQ2.2 independently contributes outside of its contribution of more beta2 to the DQ2.5 heterodimer. The other explanation is that Beta7 (*0301) cannot pair with Alpha2; however there is a DQ7.2cis haplotype. So it seems that DQ2.2 can add its own contribution.
 * DQ2.5cis/DQ2.5cis - double homozygotes - 36%
 * DQ2.5cis/DQ2.2cis - single homozygotes - 22%
 * DQ2.5cis/DQ7.5cis - single homozygotes - 3%
 * DQ2.5cis/DQ8.1cis - double heterozygote - 6%
 * DQ2.5/other - 33%
 * DQ8.1/other - 0%

The paper that investigates this is Qiao et al. 2005  (freely available). See image above on 33mer. There are 3 gliadin T-cell sites in 33mer. This paper looked at these sites IC-50 (micromolar) -stronger binding is lower. DQ2.5 DQ2.2 α-I     3.5    22 α-II    19     42 α-III    8     60 However DQ2.2 binds substantially better to the sites within the 27mer of γ5-gliadin (to premature to add to main) γ-I     4.3   8.8 γ-II    2.5   8.9 γ-IV    6.4   2.7 Therefore the role of DQ2.2 in DQ2.2 double homozygotes may be to present a γ5-gliadin site analogous to a2 gliadin's 33mer to the immune system, less efficient relative to DQ2.5-33mer, but efficient enough in some people to cause disease. In single homozygotes DQ2.2 maybe adding reactivity to other gliadins that increases risk of disease and decreases threshold. In EATL the increase in homozygotes (DQ2 only) to 70% may see the contribution of DQ2.2 as well as DQ2.5 as a factor. I can add to this two other genetics papers that outline the significance of DQA1*0201:DQB1*0202 (not DQ2.5) in Southern Europeans. This is currently what discriminates DQ2.2 from DQ2.5 mediated responses. This is not mainpage material but the reasoning why DQ2.5 needs to be discriminated from DQ2.2. See also -. These studies highlight the danger or relying to heavily on the genetics and immunochemistry entirely from one region of the world. In the case of celiac disease the involvement of DQ2.5 is profoundly greater than all other types, but in other regions of the world its involvement can take a back seat. In the second study DQA1*0201 is negatively associated with coeliac disease, whereas DQ8 dominates over DQ2.5. Of course the chileans did not move to become susceptible, the wheat moved.PB666 yap 02:24, 24 July 2008 (UTC)

Rewrite
The majority of the proteins in food responsible for the immune reaction in coeliac disease are the prolamins. These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to proteases and peptidases of the gut. One region of α-gliadin stimulates membrane cells, enterocytes, of the intestine to allow larger molecules around the sealant between cells. Disruption of tight junctions allow peptides larger than 3 amino acids to enter circulation. Membrane leaking permits peptides of gliadin that stimulate two levels of immune response, the innate response and the adaptive (T-helper cell mediated) response. One protease resistant peptide from α-gliadin contains a region that stimulates lymphocytes and results in the release of interleukin-15. This innate response to gliadin results in immune system signaling that attracts inflammatory cells and increase the release inflammatory chemicals. The strongest and most common adaptive response to gliadin is directed toward a α2-gliadin fragment of 33 amino acids in length. The response to 33mer occurs in most coeliacs who have a DQ2 isoform. This peptide, when deamidated by tissue transglutaminase, has a high density of overlapping T-cell epitopes. This increases the likelihood that the DQ2 isoform will bind and stay bound to peptide when recognized by T-cells. Gliadin in wheat is the best-understood member of this family, but other prolamins exist and hordein (from barley), and secalin (from rye) may contribute to coeliac disease. However, not all prolamins will cause this immune reaction and there is ongoing controversy on the ability of avenin (the prolamin found in oats) to induce this response in coeliac disease.

"Notes: The first sentence was changed to include peptidase and the reference to the Green review was added, along with the vH&W reference. I am leaving the reference to the Lammers et al for now, but the image has been removed, for now. The contentious discussion of the DQ2.5 isoform which is contrasted to the erroneously used the DQ2 heterodimer used in most reviews. As stated, I have a big problem with this phrase because it erroneously implies there is only one DQ2 isoform, and that only one DQ2 isoform is involved in coeliac disease, both of which are false. While the contribution of DQ2.2 is minor, it does exist and does contribute to 1% of disease. However, I have no problem with a DQ2 isoform, so I replace the article the with a and heterodimer with isoform and removed DQ2.5 from the discussion, except through a link to the DQ2 page. In the the discussion with JFW, it became clear that the nomenclature is formidable, so that keeping it simple on this main page is the best answer. And if people are curious they can follow the link to DQ2.5 and gluten where the terminological issues are explained. I have removed the mention of gamma-gliadin, while I think it will eventually end up on the page, the fact that it is not clear at the moment what the major determinants are in DQ8 and DQ2.2 mediated disease are, I can afford to leave it. However I must say that dropping that mention drops the reference to all those epitopes in barley and rye that really deserve referencing. I have therefore move the reference to the end of that sentence for now. Given that this is mentioned in reviews but not described I think it is acceptable to add the second reference." --PB666 yap 14:45, 27 July 2008 (UTC)

Reviews
- a review in Blood on the haematological complications. May be used to update the relevant content. JFW | T@lk  13:53, 21 July 2008 (UTC)


 * That paper cites a potentially useful paper - a systematic review on all serology tests. Probably worth looking at. JFW |  T@lk  14:13, 21 July 2008 (UTC)


 * Actually, he entire supplement in that issue of Gastroenterology is on coeliac, and is free (TOC of issue) - although it requires jumping through some hoops. Wish I'd known about that previously... JFW | T@lk  14:30, 21 July 2008 (UTC)


 * is a recent (2008) review from a dietetic perspective. I cannot access the fulltext, but clearly this is a good source to settle any issues we might still have about the use of oats. JFW | T@lk  16:03, 21 July 2008 (UTC)


 * A relatively insightful review. Lots of information on EATL. The other NEJM review posted by I-I has also a nice section on RCD distinction and EATL.PB666 yap 19:41, 21 July 2008 (UTC)

The devil is in the details
Reading through the pathophysiology section I must say that this appears to have far too much detail. This is an article intended for the interested general reader, not a literature review for specialists. Sentences such as "Among the 6% of European celiacs that do not have DQ2.5(cis or trans) or DQ8, 4% are DQB1*0202 and 2% DQA1*05, 0.4% cannot be linked to DQ8, DQA1*05, or DQB1*02" will add little value for the vast majority of our readers. Simplifying this section, and presenting a summary of the known facts, rather than excessive detail on current research, could solve this problem about which sources to use and have the added benefit of making the article more readable. If I find this tough going and I've got a PhD in biochemistry, that is a pretty clear indication that you've missed your intended audience by a wide margin. Tim Vickers (talk) 18:18, 22 July 2008 (UTC)


 * Yes, I will rewrite that sentence. I believe the sentence is important because some celiacs claim they are DQ2 negative, DQ8 negative and they claim they are neglected by genetic analysis. The particular study reference shows that around 2% of patients are not DQ2 or DQ8, and can still have CD. I think the end of the sentence can read "4% have the DQ2.2 isoform and the remaining 2% lack DQ2 or DQ8 in any form." (I should point out from censored comments, that 1% have only the DQ2.2 isoform as they are DQA1*0201:DQB1*0202 homozygotes). I don't think, with studies in hand on single homozygotes and the low level (1.6%) of DQA1*0505 that this allele needs to be given special consideration, I retained it for accuracies sake. In the single homozygotes DQ2.2/DQ2.5 dominates, there are very few DQ7.5/DQ2.5 within that set. Both VH&W and Karell create a great dependency on the European wide study. This is important because there is a problem. When I originally wrote the genetics section I discounted the role of DQ2.2 and was in agreement that there was a single DQ heterodimer involved. With Karell, however, this notion becomes untenable. Apparently, in Northern Europeans there are very few coeliacs without DQ2.5-"the DQ2 heterodimer" or DQ8 and most of the early DQ studies were on Northern Europeans. However, in Southern Europe they have detected a sizable fraction with DQ2.2  "the other DQ2 heterodimer".(See table up the Talk page) For this reason, recently, researchers have adopted the new terminology, DQ2.5 and DQ2.2 (and very recent papers are using DQ2.5cis and DQ2.5 trans to differentiate between α5-β201 and α5-β202). To date only two papers have singled out DQ2.2 (α2-β2) for study, and none of this material has been secondary sourced. For this reason, I suggest we rely on Karell as a primary source of information, and in Karell they describe the source of these genetic outlyers, most of which come from Southern Europe.
 * The other genetic linkages Celiac 2 ~ 5 appear not to be supportable within the literature. I have wanted to remove the last paragraph in the genetics section for some time. If we can agree that there is alot of contradictions about these other genetic loci to the point of removing that paragraph.PB666 yap 13:18, 23 July 2008 (UTC)


 * How about removing the paragraph on C2-5 and putting it here on the talkpage for discussion? JFW | T@lk  14:09, 23 July 2008 (UTC)


 * I refrain from removing anything on the main page without discussion, I have left the following intactPB666 yap 17:10, 23 July 2008 (UTC)


 * "Among the 6% of European celiacs that do not have DQ2.5(cis or trans) or DQ8, 4% are DQB1*0202 and 2% DQA1*05, 0.4% cannot be linked to DQ8, DQA1*05, or DQB1*02.[31]"
 * "The frequency of these genes varies geographically. DQ2.5 has high frequency in peoples of North and Western Europe (Basque Country, Ireland,[32] with highest frequencies), portions of Africa, and is associated disease in India,[33] but is not found along portions of the West Pacific rim. DQ8, spread more globally than DQ2.5, is more prevalent from South and Central America (up to 90% phenotype frequency).[34]"


 * "In addition to the CELIAC1 locus, CELIAC2 (5q31-q33 - IBD5 locus), CELIAC3 (2q33 - CTLA4 locus), CELIAC4 (19q13.1 - MYOIXB locus), have been linked to coeliac disease. The CTLA4 and myosin IXB genes have been found to be linked to coeliac disease and other autoimmune diseases.[35][36] Two additional loci on chromosome 4, 4q27 (IL2 or IL21 locus) and 4q14, have been found to be linked to coeliac disease.[37][38]]|undefined"


 * My comment is that the only article here that has been recently reproduced is 4q27, and only by the same author who produced the association. My worry about this is that there appears to be diagnosis bias. People who were drafted into these studies were not randomly detected celiac disease, but people whose coeliac diagnosis was secondary to a common autoimmune disease (t1D, Grave's, Hashimotos, etc). Many of the markers hit are identified as markers for these other autoimmune disease. I suspect the reason the genetic associations, always weak, vary depends on the emphasis in different clinics placed on testing diseases associated with celiac disease.PB666 yap 17:10, 23 July 2008 (UTC)

I have made the changes to the Genetics section requested, I have also removed the section of Celiac1 to Celiac 5 genetics and I have placed a copy of the removed material on a personal page so that if we need to add this material back at some point, part or all, then we don't have an awkward revert.PB666 yap 18:19, 27 July 2008 (UTC)


 * I have to say, I tend to agree with Tim Vickers; the pathophysiology section is becoming too dense with details that the target audience are not likely to understand, and perhaps will have little interest in. The coeliac disease article is an FA level article that is meant to read well to a general non-scientific audience, and may risk losing this level with the poorly (I'm sorry - it is not easy to follow) explained HLA types and confusing details about linkage. Looking from another viewpoint though, as a scientist who often needs to know the details of HLA types at high resolution (i.e. with at least a four number classification) for investigating disease association(s), the information given in this section perhaps should not be removed, rather budded off to a sub-article dealing with disease associations to given HLA molecules.
 * There would be a small number of folks, I'm sure, that would be interested in this more complex information and would be able to more accurately interpret/evaluate conflicting reports in the literature. A link to the sub-article could be created under the header of that section. That way, the genetics part of pathophysiology section would not dominate the article, as it is in danger of doing with all the proposed additional information. What do other people think? ~ Ciar ~  (Talk to me!)  19:32, 27 July 2008 (UTC)


 * These are not proposed additions, that section already exists on the page, and I was talking about removing the last 2 sentences, which has already been done. I have no current intent on expanding the genetic section, and I think it would be great at some point to have another subpage, but not right now. Primary issue is the immunochemistry. The genetics section as it stands has been apart of FA twice. The genetics section has been getting smaller, ever so slowly.
 * The four numbering system is a pain in the rear-end, there are only 9 DQ serotypes and with the exception of DQ6 there are fewer than 10 antigens. You cannot neccesarily tell looking at the number whether two genes produce identical proteins or not, but unfortunately, mistakes have been made by abbreviating information. We (mostly I) have been whittling away at the section since it was rewritten. The transglutaminase section needs to be drawn down, however, I am not undertaking any other projects on Coeliac page at the moment because there are 2 other pages that I created that need serious fixing. I don't think the genetics part dominates the article, but FYI coeliac disease has one of the strongest genetic linkages of any autoimmune disease, therefore its a dominant force in the article because its a dominant factor in disease (other than wheat). Even if you leave off the part about DQ8-,DQ2- disease someone will claim their little subset of coeliac disease has been ignored.PB666 yap 02:22, 29 July 2008 (UTC)

Indo-European
This term refers to language and culture, not genetics, and should not be used here. Caucasian? Brownturkey (talk) 09:41, 3 August 2008 (UTC)


 * I will give you a short answer, you are right, but incredible as it may seem, coeliac disease tends to follow where IE languages are spoken. IE language is the language of post-neolithic wheat spread in much of the world. This spread pushed wheat culture into genetically susceptible populations who either ate largely barley, rye, or emmer's and einkorn wheat. In Ireland for example barley was primarily grown for fermentation or malting and they ate the meat of animals such as cattle. This process began only a few thousand years ago. Possibly around the time when the earliest Celtic languages spread into Western Europe. Barley is really low in protein and does not have the most toxic peptides, and fermentation destroys much of these. The same pattern of use was seen in Northern Britain and Scandinavia.. a little Wheat, Barley and recently rye use, mostly for cattle. These areas of Europe are high in DQ2.5 and thus the pushing of Mediterranean culture into these areas of Europe caused that risk to increase. As Europeans spread the brought with them DQ2.5, for example it is very high in Australia now, peoples from places wheat was not grown to places where it is the dominant staple. IE languages areas have elevated DQ2.5 relative to Arabic areas, Arabic speakers have reduced risk because they have grown wheat for the last 10,000 years, evolution-negative selection. The same is also true for Eastern Afro-asiatic speaking Africans, but not for western Africans.


 * One part of the answer to coeliac disease genetics- for people who are DQ2.5 homozygotes who eat wheat as a staple, are any other genetic factors required. Given the latest data from Finland, it does not seem likely. DQ2 homozygotes almost make a majority of disease in some areas. The random frequency of DQ2 homozygotes that are most susceptible is F = f(DQ2.5)^2  + 2*f(DQ2.2)*f(DQ2.5) or, roughly, F = 3/4 * f(DQ2)^2 when f(DQ2.5)~=f(DQ2.2). Basically as DQ2.5 doubles, homozygote frequencies quadruple when DQ2.5 is present and DQ2.2 frequency grows, homozygote frequencies double. In parts of Spain and the Ilse that frequency reaches 35%hz, in parts of the middle east that frequency is 2%hz. Within this select group of people the risk around midlife is around 15%. As you can imagine that cause the risk of disease in the DQ2 homozygote rich group to soar. However in places where few homozygotes are found (DQ2.5 is low or DQ2.2 is low) that risk cuts the rate almost in half. Interestingly where the frequencies of DQ2.5 and DQ8 peak in the world, wheat consumption decreases. In the Americas, DQ8 peaks in the Aché, they left French protection and returned to the jungles, and the Lacandon Mayan, who retain their indigenous customs represent the highest DQ-type frequency for any group of people in the world. The peak of DQ2.5 is in Western Ireland, which has not traditionally grown or consumed large amounts of wheat. Dog wagging tail or tail wagging dog?  I can give you a more detailed risk analysis, but as that depressive robot -Marvin-  says 'you wouldn't like it'. PB666 yap 20:16, 3 August 2008 (UTC)

Genetics Section
"Sentences such as 'Among the 6% of European celiacs that do not have DQ2.5(cis or trans) or DQ8, 4% are DQB1*0202 and 2% DQA1*05, 0.4% cannot be linked to DQ8, DQA1*05, or DQB1*02' will add little value for the vast majority of our readers. Simplifying this section, and presenting a summary of the known facts, rather than excessive detail on current research, could solve this problem about which sources to use and have the added benefit of making the article more readable." The comment made by Tim Vickers suggests that more simplification or clear rewrite may be neccesary. My original intent was to convey the material while not creating inaccurate information. The debate, largely refactored, indicates that there may be a way of simplifying the section. The whole Pathophysiology section is troubled, the lead is not balanced, the prolamin section was worded so that it avoids certain lingo, the transglutaminase section needs to be cut back to secondary sourced material. Since the majority of complaints are about the genetics section and the lead I will focus on this first. It will take me some time. I am not downplaying the comments, simply stated for every dumbing-down of information on this page I think it is best to have a clarifying recipient on another page if details are warranted.PB666 yap 16:57, 4 August 2008 (UTC)

AH8.1
I am going to keep this short, some here may be interested. AH8.1 (alias "super B8") haplotype is found in Irish, Scandinavians, Basque, Swiss, Scottish, Welsh, Cornish, Icelandic, Hungarians, Serbians, Pomers. It is the most common haplotype in Europeans with Peak frequency is in the Western Irish at >11% and recombination is slow, though marked. Its evolution differs from expectation by two magnitudes. AH8.1 may be the reason why other autoimmune genes associated with celiac disease are hard to find. The haplotype is 4.8 million nts in length, in a highly variable region of the human genome, it is highly remarkable that it is the longest haplotype known, covering 271 transcript encoding genes.. These papers raise an extreme possibility that genes close (telomeric) to HLA-DRB1 may confer increased susceptibility to autoimmunity with DQ2.5 and peoples of Western or Northern European ancestry. Given these new studies it may be possible to segregate more carefully controls and better determine risk in Europeans. The evolutionary context of AH8.1 is something of great concern now, it is almost certain that strong selective factors have guided the evolution of this and 2 other types. Since this is about food culture and selection, the importance of AH8.1 becomes all the more important object of study. Two other papers,, talk about splicing of DQA1*0501, potentially may help understand why DQB1*0505 is less associated with disease relative to DQB1*0202.PB666 yap 22:08, 8 August 2008 (UTC)

Infection risk
- primary research study showing increased risk of infection 20-90%. JFW | T@lk  20:41, 18 August 2008 (UTC)
 * Parts of AH8.1 are involved in altered immune response as seen in HIV and a few other diseases. The affected loci are between A1 and DR3. The authors of the paper did not haplotype determination in any of the controls, however we can deduce that ~15% of the coeliacs are AH8.1 homozygotes. This means there is a high prevalence of:
 * IgA absent phenotype
 * C4A (null)
 * One can assume that less than 1% of the controls have this phenotype. Other risk factors can be found: HLA-A1, HLA A1-B8 haplotype
 * The authors of the paper mention that they do not parse out the following conditions:
 * Refractory Celiac Disease 1 or 2 (Nor did they parse out drug treatment and risk)
 * Lymphoid cancers (increased risk in celiacs)
 * While the paper has a powerful population parameter, it lacks the appropriate use of controls with regard to HLA, they should have looked at HLA matched controls, also, and they should have treated refractory or secondary conditions separately.PB666 yap 16:10, 26 August 2008 (UTC)
 * Note: Risk of full AH8.1 homozygotes in coeliac disease for scandinavia is approximately 15% x 0.57 x 0.57 = 5.0%. For the general population it is only about 0.3%

Modified Marsh
There is a "modified MARSH classification" from modern pathology 2002 that I believe is currently used in the medical community. Please review.

Type Lymphocytes per 100 Enterocytes Crypts Villi

0 <40 Normal Normal 1 >40 Normal Normal 2 >40 Increased Normal 3a >40 Increased Mild atrophy 3b >40 Increased Marked atrophy 3c >40 Increased Absent

This is the reference if anybody is interested.

Mod Pathol 2003;16(4):342–346 Celiac Disease: A Progress Report Donald A Antonioli M.D.1

199.212.7.17 (talk) 18:24, 10 October 2008 (UTC)


 * Do you have any evidence that this is now the favoured system? JFW | T@lk  19:49, 11 October 2008 (UTC)


 * IEL are not a specific diagnostic criteria for CD. If one wishes to discuss the loose collection of associations with stage 1 and 2 disease I will be happy to provide references on my talk page. To summarize, the power of the studies done so far are not great. The demostration of elevated IEL in stage 1 and 2 were retrospective studies of patients who were diagnosed with CD and had biopsies taken years before diagnosis. To translate - the appearance of elevated IEL in some people fortells progression to CD. IEL, however are found in other inflammatory diseases that do not progress to CD.PB666 yap 23:58, 3 November 2008 (UTC)

External Links Questions
Hi - i'm confused as to why an external link like celiac.com can be listed on this article. Celiac.com has advertising and sells products. I would like to add an external link which offers free recipes, celiac disease information and gluten free diet resources. The site is elanaspantry.com and it is non-commercial and ad-free. if i cannot add this link, can someone please explain as to why? also, why a commercial site like celiac.com can remain? thanks! Gfstephen (talk) 18:55, 4 November 2008 (UTC)


 * This has already been explained to you. It has also been explained to your other single-purpose account Elanaspantry (talk · contribs) -- This link and celiac.com have been removed per WP:EL guidelines.  Thanks!   coccyx bloccyx  (toccyx)  19:23, 4 November 2008 (UTC)


 * Thanks for all your help in this matter! Gfstephen (talk) 19:35, 4 November 2008 (UTC)

Recent review by Barker & Liu
A new review of coeliac disease is out: I just now used it to improve Epidemiology, but I think it could be used elsewhere in the article too, to address WP:WEIGHT issues and the like. Eubulides (talk) 18:59, 11 December 2008 (UTC)


 * Care to inform us where the article has WEIGHT issues? JFW | T@lk  21:48, 11 December 2008 (UTC)


 * I'd love to, but I don't know. I'd have to read Coeliac disease and Barker & Liu carefully first. So far, I've carefully read only the epidemiology sections of both. I was hoping a coeliac expert could take it from here (yes, I know, there are dozens and dozens of those with lots of free time on their hands at Wikipedia....). Eubulides (talk) 06:52, 12 December 2008 (UTC)


 * When this article was promoted to featured article in 2007 it was reviewed by an expert. The talk page archive will show that. We have no duty Wikipedia gastroenterologist or paediatrician at the moment, let alone a coeliac expert.
 * Talking about reviews, has appeared today. JFW |  T@lk  07:10, 12 December 2008 (UTC)
 * Sheesh, that new one is not even in PubMed yet; how'd you find it? I added a citation to it, again to Coeliac disease, even though that review's strengths are more in the area of diagnosis. Anyway, it sounds like there aren't major weight issues; sorry to raise any false alarm in that area. I hope my additions to Epidemiology haven't bloated that section beyond what an expert would think appropriate. (One of my many weaknesses is a fondness for epidemiology.) Eubulides (talk) 21:51, 12 December 2008 (UTC)

Please let me know if there are other weaknesses in the article. I would need copies of both reviews to work any relevant material into the article. There is nothing at all wrong with a strong and broad epidemiology setting; for most diseases, there is so little information available as it is! By the way, I spotted the BMB review because I've subscribed to its emailed table of contents! JFW | T@lk  01:10, 14 December 2008 (UTC)