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Symptoms
Autoimmune diseases present similar symptoms across the more than eighty different types. The appearance and severity of these signs and symptoms depends on the location and type of autoimmune response that occurs. An individual may also have more than one autoimmune disease simultaneously, and display symptoms of multiple diseases. Signs and symptoms presented, and the disease itself, can be influenced by various other factors such as age, hormones, and environmental factors. In general, the common symptoms are:


 * Fatigue
 * Low grade fever
 * General feeling of unwell (malaise)
 * Muscle aches and joint pain
 * Rash on different areas of the skin

The appearance of these signs and symptoms can fluctuate, and when they reappear, it is known as a flare-up. Such signs and symptoms may aid in diagnosis by supporting the results from biologic markers of autoimmune diseases.

There are several areas that are commonly impacted by autoimmune diseases. These areas include: blood vessels, underlying connective tissues, joints and muscles, red blood cells, skin, and endocrine glands, like thyroid or pancreas glands.

These diseases tend to have characteristic pathological effects which characterize them as an autoimmune disease. Such features include damage to or destruction of tissues where there is an abnormal immune response, altered organ growth, and altered organ function depending on the location of the disease. Some diseases are organ specific and are restricted to affecting certain tissues, while others are systemic diseases that impact many tissues throughout the body. Signs and symptoms may vary depending on which of these categories an individual’s disease falls under.

Causes
While the underlying cause of symptoms has been identified to be a compromised immune system, science is relatively uncertain of what may lead to this. Due to recent breakthroughs in technology, it is becoming easier to identify possible causes thus, a list of highly suspected contenders is acknowledged by the scientific community. From this list, the most widely researched and suspected agents including genetic and environmental factors.

Genetic Factors :
Autoimmune diseases are conditions in which the human immune system attacks healthy human tissues within the body. The exact genes responsible for causing each autoimmune disease have not been completely isolated. However, several experimental methods such as the genome-wide association scans have been used to identify certain genetic risk variants (A. Immunol, 2010) (11). Research focusing on both genome scanning and family trait inheritance analysis has enabled scientists to further understand the etiology of autoimmune diseases such as Type 1 diabetes and Rheumatoid arthritis (N. Hill, 2008) (2).


 * Type 1 Diabetes: Type 1 Diabetes (T1D) is a condition in which pancreatic β-cells are targeted and destroyed by the immune system (Molven, 2008) (5).  Approximately 5% of the U.S. population are recorded to have T1D (Menke, 2013) (12). The condition is a result of neo-natal mutations to the insulin gene (INS) which is responsible for mediating the production of the insulin in the pancreas (Molven, 2008) (5).  The INS gene is located on the short arm of chromosome 11p15.5 in between the genes for tyrosine hydroxylase and insulin-like growth factor II (S. Bennett, 1996) (4).  The loci for this gene was determined using human-mouse somatic cell hybridization as well as In Situ hybridization (Bennet, 1996) (4).  In addition to chromosome 11, a significant genetic determinant of type 1 diabetes is a locus called the major histocompatibility complex (MHC) located on chromosome 6p21 (N. Hill, 2008) (2).  The two genetic variables that influence susceptibility to T1D are the INS gene on chromosome 11 and the MHC loci on chromosome 6.


 * Rheumatoid arthritis: Rheumatoid arthritis (RA) is an autoimmune disorder that affects approximately 0.6% of the population in the U.S. (F. Kurreeman, 2007) (9).  The disease is an inflammatory condition that typically affects the joints, but is also known to cause tissue damage to other organs of the body.  Although there is no complete genetic mapping for this condition, several genes are thought to play a role in causing RA. The genes that influence the human immune system contains a TNF receptor associated factor 1(TRAF1).  This TRAF1 is located on chromosome 9q33-34 (F. Kurreeman, 2007).  In addition, B1 genes in the human genome contain an increased concentration of HLA-DRB1 alleles that are most commonly seen in RA patients (C. Weyand, 1995) (8).  RA can range from mildly dangerous to life threatening in different individuals suffering from the condition as a consequence of varying polymorphisms within the genome (C. Weyand, 1995).  As a result, the nature and severity of RA is heavily influenced by the human genome and the mutations or chemical abnormalities within it.

Environmental Factors :
A range of environmental factors have been recognized as either having a direct role in development, or being a catalyst to many autoimmune diseases. Current studies indicate up to seventy percent of autoimmune disease are due to environmental factors, including: chemicals, infection, diet, and gut dysbiosis. A single set of steps has been identified to be the most likely theory for Autoimmune Disease onset.


 * 1) Environmental Triggers
 * 2) Reduced Oral Tolerance
 * 3) Gut Dysbiosis
 * 4) Enhanced Gut Permeability
 * 5) Increased Immune Reactivity
 * 6) Autoimmunity

Chemicals can be found within the direct environment or in the form of drugs, including: hydrazines, hair dyes, trichloroethylene, tartazines, hazardous wastes, and industrial emissions (I). UV radiation is found to be a possible cause of development of  the autoimmune disease dermatomyositis, exposure to pesticides plays a role in rheumatoid arthritis development , and vitamin D has been found to be a key in preventing immune dysfunctions in older populations. Infectious agents are considered T cell activators, a step needed for activation of autoimmune diseases. These mechanisms are relatively unknown, but are one of the current theories to explain autoimmune diseases triggered by infection such as Guillain-Barre syndrome and rheumatic fever.

Theories :

 * Cryptic determinants/molecular sequestration

Although it is possible for a potential auto antigen to be spatially sequestered in an immune-privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system. However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an auto antigen. This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance. These poorly displayed areas of an antigen are called "cryptic determinants." The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.


 * Molecular mimicry

The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self. The cross reactive immune response is ++responsible for the autoimmune disease state. Cross-reactive immune responses to self were first described for antibodies.


 * Altered glycan theory

According to this theory, the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.


 * Hygiene hypothesis

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune or allergic conditions such as asthma

Diagnosis
For a disease to be regarded as an autoimmune disease it needs to answer to Witebsky's postulates:


 * Direct evidence from transfer of disease-causing antibody or disease-causing T lymphocyte white blood cells
 * Indirect evidence based on reproduction of the autoimmune disease in experimental animals
 * Circumstantial evidence from clinical clues

Symptoms of early autoimmune disease are often the exact same as common illnesses, including: fatigue, fever, malaise, joint pain, and rash. Due to the fact symptoms vary for affected location, disease causing agents, and individuals, it is difficult for proper diagnosis. Typically, diagnosis begins with looking into a patient’s family's history for genetic predisposition. This is combined with various tests, as no single test can identify an autoimmune disease.


 * Antinuclear Antibody (ANA) Test: A test used to identify abnormal proteins, known as antinuclear antibodies, produced when the body attacks its own tissues. A patient's blood is used for this test, and can test positive for several disorders. This test varies with success, as some diseases have varying success rates. This test is most useful for diagnosing systemic lupus erythematosus, having a 95% positive test rate. A test is considered positive if there is a large amount of antinuclear antibodies, or specific patterns of cellular fluorescence seen within the patient's blood.


 * Complete Blood Count Test(CBC) : A test taking measurements on maturity levels, count, and size of blood cells . Targeted cells include: red blood cells, white blood cells, hemoglobin, hematocrit, and platelets. Based on increased or decreased numbers in these counts, underlying medical conditions may be present; typically, autoimmune disease is represented by low white blood cell count (Leukopenia). For proper diagnosis, further testing is needed.
 * Complement Test : A test used to measure levels of a protein group of the immune system called complement within blood. If complement is found in low levels, this may be an indication of disease.
 * C Reactive Protein Test(CRP) : A test measuring levels of C reactive protein, a protein made in the liver. Higher levels may indicate inflammation, a common symptom of autoimmune disease.
 * Erythrocyte Sedimentation Rate Test(ESR) : This test measures the rate at which a patient’s blood cells descend in a test tube. More rapid descents may indicate inflammation, a common symptom of autoimmune disease.

If these tests are indicative antibody abnormalities and inflammation, further tests will be conducted to identify the autoimmune disease present.

Treatment
Treatment depends on the type and severity of the condition. The majority of the autoimmune diseases are chronic and there is no definitive cure, but symptoms can be alleviated and controlled with treatment. Overall, the aim of the various treatment methods is to lessen the presented symptoms for relief and manipulate the body’s autoimmune response, while still preserving the ability of the patient to combat diseases that they may encounter. Traditional treatment options may include immunosuppressant drugs to weaken the overall immune response, such as:


 * Nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation
 * Glucocorticoids to reduce inflammation
 * Disease-modifying anti-rheumatic drugs (DMARDs) to decrease the damaging tissue and organ effects of the inflammatory autoimmune response

Other standard treatment methods include:


 * Vitamin or hormone supplements for what the body is lacking due to the disease (insulin, vitamin B12, thyroid hormone, etc.)
 * Blood transfusions if the disease is blood related
 * Physical therapy if the disease impacts bones, joints, or muscles

Because these drugs aim to reduce the immune response against the body’s own tissues, there are side effects of these traditional treatment methods, such as being more vulnerable to infections that can potentially be life threatening. There are new advancements in medicine for the treatment of autoimmune diseases that are currently being researched, developed, and used today, especially when traditional treatment options fail. These methods aim to either block the activation of pathogenic cells in the body, or alter the pathway that suppresses these cells naturally. The goal for these advancements is to have treatment options available that are less toxic to the patient, and have more specific targets. Such options include:


 * Monoclonal antibodies that can be used to block pro-inflammatory cytokines
 * Antigen-specific immunotherapy which allows immune cells to specifically target the abnormal cells that cause autoimmune disease
 * Costimulatory blockade that works to block the pathway that leads to the autoimmune response
 * Regulatory T cell therapy that utilizes this special type of T cell to suppress the autoimmune response