Autoimmune diseases are a group of disorders where your immune system malfunctions and attacks your own tissues. One aspect of these diseases is the formation of antibodies that are directed to self-antigens (autoantibodies). Autoimmune diseases can be divided into two general groups: Organ specific, where the autoantibodies attack a specific organ, and Non-organ specific (or systemic), where the autoantibodies attack multiple organ systems. An example of an organ specific autoimmune disease is Hashimoto’s thyroiditis where autoantibodies damage the thyroid gland. An example of a systemic autoimmune disease is Systemic Lupus Erythematosus (SLE) where the autoantibodies can attack any organ in the body.
The systemic autoimmune rheumatic diseases (SARD) are a group of systemic autoimmune diseases that include: Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) (and subsets of Lupus), Sjögren’s syndrome (SjS), Systemic Sclerosis (SSc), Polymyositis (PM) and Dermatomyositis (DM). Rheumatoid arthritis is the most prevalent disease in this group; however, the ANA assay is not the primary laboratory test for RA. Instead, the diagnostics for RA look for the presence of Rheumatoid Factor (RF) antibodies or more currently anti-cyclic citrullinated peptide antibodies (CCP). For the other diseases in the SARD group, especially SLE and SSc the results of the ANA test can be critical in determining a correct diagnosis.
The Antinuclear Antibody test (ANA) is a test used to screen for the presence of autoantibodies that are directed to components in the nucleus of the cell. Clinicians use the ANA test to assess the likelihood that a given patient has a SARD.
The SARD’s are just one subset of diseases caused when immunological tolerance of our own tissue is somehow lost and our immune system begins to attack our own tissues in the same manner that it would a foreign antigen.
Why our immune system malfunctions is not completely understood. One current hypothesis is that a series of events occurs resulting in the initiation of an autoimmune reaction.
The first step in this process is genetic susceptibility. The genotype of some individuals predetermines that their immune system will be more prone to a break in tolerance. This genetic susceptibility appears to be linked to multiple genes rather than a single gene. This is supported by evidence that some autoimmune diseases are more frequently encountered in certain ethnic groups compared to others. For example in American women between the ages of 15 and 64 the prevalence of SLE is 1 in 700 for Caucasians while it is 1 in 245 for African-American women (1). Evidence in one recent study suggests that the genes that impart an increased resistance to malaria unfortunately produce an increased susceptibility to the SARD’s (2). Additionally, women are more likely to develop an SARD. For example in SLE the female to male ratio is 9:1.
The second step is the occurrence of a triggering event that leads to a break in tolerance. For some very susceptible individuals this trigger event might be exposure to an environmental trigger. These environmental triggers could be ubiquitous such as exposure to the Epstein Barr virus (EBV), or very limited such as the controversial exposure to leaking silicon from a breast implant. In others, the triggering event might be a change in hormonal balance. Whatever the case, the triggering event initiates the break in tolerance and the cascade of immunological events that eventually lead to the formation of an autoimmune disease begins.
The third step is the development of autoantibodies and subsequent development of clinical symptoms. Studies have shown that this process can take 3 years or longer and unfortunately by the time the diagnosis is made substantial damage to the body has already occurred.
The utility of the ANA test is to detect the antibodies early in the disease process. The ANA results in conjunction with clinical presentation give the clinician solid evidence to intervene with an appropriate treatment. Studies have shown that once treatment is started the formation of new antibodies slows or even halts (3).
Currently there are no cures for the SARD’s. Treatments primarily focus on keeping the patient comfortable and the immune response in check. Treatments can vary from non-steroidal anti-inflammatory drugs, to immuno-suppressive drugs, to stem cell transplants. One’s individual treatment is often dependent on the severity of the disease and the response to the selected drug regimen.1. Sullivan KE. The complex Genetic Basis of Systemic Lupus Erythematosus, Reprint from 1999 and 2000; Lupus Foundation, Available at http://www.lupus.org/education/articles/geneticbasis.html Accessed June 16, 2010. 2. Willcocks LC, Carr EJ, Niederer HA, et al. A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus. Proc Natl Acad Sci U S A. Apr 27 2010;107(17):7881-7885. 3. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. Oct 16 2003;349(16):1526-1533.