Ana-Maria Orbai, M. Rheumatologists specialize in diagnosing and treating musculoskeletal diseases and autoimmune conditions rheumatic disease. Orbai talks about how to recognize common autoimmune disease symptoms and when you should see a doctor. There are more than 80 types of autoimmune diseases that affect a wide range of body parts. Symptoms of autoimmune disease may be severe in some people and mild in others. Despite the varying types of autoimmune disease, many of them share similar symptoms.
Common symptoms of autoimmune disease include:. You have to have certain symptoms combined with specific blood markers and in some cases, even a tissue biopsy. Diagnosis can also be difficult because these symptoms can come from other common conditions. Orbai says women should seek treatment when they notice new symptoms.
For example, in systemic lupus erythematosus , over 80 genes have been identified in each of our 22 plus XY chromosomes, as nicely illustrated in this drawing from Chen L et al, Curr Opin Rheumatol, Since autoimmune disease genes are many and individually have low impact, they have been particularly challenging to study.
In a handful of cases, autoimmune diseases are monogenic, that is arise from defects in a single gene. Although rare, these monogenic autoimmune diseases have yielded fantastic insights into autoimmunity because disease manifestations are easier to understand when deriving from a single defect.
Five examples of autoimmune diseases caused by a single gene defect are shown in the table below. APS-1 is characterized by at least two of three clinical features: muco-cutaneous candidiasis, Addison disease, and hypoparathyroidism.
Patients also have many additional organ-specific autoimmune diseases such as thyroiditis, type 1 diabetes, vitiligo, autoimmune gastritis, premature ovarian failure, testicular failure, etc. There is great variability in the types of autoimmune diseases patients with APS-1 develop, as well as in the time these diseases develop, even when the AIRE mutation is the same and patients belong to the same family.
AIRE plays a key role in establishing tolerance to self-antigens. AIRE is expressed in the nucleus of medullary epithelial cells in the thymus see photo of a mTEC cell with AIRE protein in red where it orchestrates the expression of peripheral self-antigens, such as insulin of the pancreatic beta cells or the acetylcholine receptor of the neuro-muscular junctions.
T lymphocytes that mature in the thymus interact with mTEC cells: if by chance T cells have an antigen receptor that binds well to these peripheral self-antigens expressed by mTEC cells they are destroyed, and therefore do not exit the thymus to become part of the T-cell repertoire we have in the blood and secondary lymphoid organs spleen and lymph nodes.
If AIRE is mutated, however, a number of peripheral self-antigens are not presented anymore on mTEC cells, and thus the T cells that recognize them are not deleted in the thymus but rather escape into the periphery where they are available to cause autoimmune diseases. Patients with autoimmune diseases have multiple defects in regulatory mechanisms that normally prevent autoreactive lymphocytes to develop or control them if they do appear in the periphery.
Numerous defects in cellular immunity have been demonstrated in animal models of autoimmune diseases or other experimental settings. Examples include decreased number or function of regulatory T cells, resistance of effector T cells to immune regulation, defective function of antigen-presenting cells such as dendritic cells and macrophages. In the clinical setting, however, these studies of cellular immunity are still not popular because of high costs, technical difficulties such as limited access to the organ targeted by autoimmunity , and overall feasibility.
Autoantibodies on the other hand and the B lymphocytes that produce them remain the main clinical indicator of an immunological dysfunction in patients with autoimmune diseases. For a long period of time, autoantibodies were considered a mere biomarker of disease and received limited attention in regards to their pathogenic role.
Recent years, however, have seen a resurgence in the interest on autoantibodies, both in terms of their diagnostic and predictive value. The presence of autoantibodies has taught us that immunological abnormalities are present years before the clinical diagnosis of an autoimmune disease. For example, antibodies to glutamic acid decarboxylase , protein tyrosine phosphatase receptor type N, and insulin predict by several years the development of type 1 diabetes in asymptomatic first-degree relatives.
Similarly, antibodies to Ro and La are present at least 5 years before the clinical diagnosis of systemic lupus erythematosus. And antibodies to thyroperoxidase precede by at least 7 years the clinical diagnosis of Hashimoto thyroiditis. These critical observations were made using the Department of Defense Serum Repository. Since , this repository stores sera of active-duty military personnel as they are collected every two years of service, and before and after each deployment. When soldiers are then diagnosed with an autoimmune disease, it is thus possible to check what was their autoantibodies status in earlier years, when they were asymptomatic and healthy.
The incidence of autoimmune diseases has increased remarkably since they were first recognized as distinct medical entities in the s. Part of the increase is undoubtedly secondary to a greater awareness in the medical community about these conditions.
But the increase is too large to be explainable only by better diagnostics. Of the three factors that contribute to the pathogenesis of autoimmune diseases genes, immune system, and environment , environment is the one where firm, scientifically sound conclusions have been the most limited.
Part of the difficulty arises from the fact that each individual autoimmune disease is not very common in the general population. This makes it very challenging to identify environmental factors associated with that disease, also because these factors are expected to confer only a small increase in risk. In addition, autoimmune diseases themselves can be difficult to categorize and define, have variable age at onset, and poorly predictable age at onset.
These difficulties have meant that pretty much every possible environmental factor, from poor air quality and pollution to the ever-elusive local viral infection, has been associated with one autoimmune disease or another. Affinity maturation: the process through which B cells mature and produce antibodies that have a greater affinity for their antigenic target.
Many scientists believe this is what causes rheumatoid arthritis, a type of autoimmune disease that attacks the joints. Other types of autoimmune disease may come from the body trying to fight specifically against cancer cells. Orbai points to scleroderma , a disease that causes thickening of the skin and connective tissues.
Johns Hopkins researchers studied patients who developed both scleroderma and cancer to try to clarify this relationship. Scientists think injury may play a role in some types of autoimmune disease such as psoriatic arthritis , a condition that affects the joints of some people with psoriasis.
Research has shown that in parts of the body subjected to high stress, an autoimmune response happens after damage to tendons, which attach muscle to bone. Blood cells try to heal it, but an abnormal immune response causes inflammation of the joints and tendons. Orbai is quick to point out that while there is some data to support them, scientists have not proven that these are causes of autoimmune disease.
For example, having a family member with lupus or multiple sclerosis MS raises your risk of getting these diseases.
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