The reason our immune system malfunctions is not completely understood. The generally accepted hypothesis is that the following factors may contribute to the initiation of an autoimmune reaction.
Gender and genetic predisposition
A predisposition is usually the first step toward the development of an autoimmune reaction. Women are more likely to develop a systemic autoimmune disease than men. The prevailing theory is that the female sex hormones and the variation of those hormones throughout life may predispose women toward autoimmunity. For example, in systemic lupus erythematosus (SLE), the female-to-male ratio is 9:1.
The genotype of some individuals may also predispose their immune system to a breakdown of self-tolerance. This genetic susceptibility appears to be linked to multiple genes rather than a single gene. Research has found an association between the presence of certain human leukocyte antigen (HLA) types and an increased risk of the development of a specific autoimmune disorder. Inherited mutations may also interfere with one or more normal immune regulating mechanisms. This is supported by evidence that some autoimmune diseases are frequently encountered within the same families; this is also true of 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 245 for African American women, whereas it is 1 in 700 for Caucasian women. Evidence in one recent study suggests that the genes that impart an increased resistance to malaria unfortunately produce an increased susceptibility to systemic autoimmune rheumatic diseases.
Triggering event
Another factor is the occurrence of a triggering event that leads to a breakdown of self-tolerance. For some very susceptible individuals, this 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 exposure to leaking silicone from a breast implant or smoking. 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 eventually leads to the formation of an autoimmune disease.
Development of autoreactive T cells, autoantibodies, or both
The final factor influencing autoimmune disease development is the production or activation of an autoreactive immune component. Autoimmune diseases may be caused by several aberrant immune mechanisms. The development of these self-reactive cells and/or antibodies are an immediate precursor to the development of clinical symptoms. Studies have shown that this process can take three years or longer, and unfortunately, by the time the diagnosis is made, substantial damage to the body may have already occurred.
It's important to note that not all individuals who have a genetic predisposition to an autoimmune disease will develop autoimmune disorders, nor can we typically determine a single triggering event. The specific events that occur to produce autoimmune disease are often unclear and are unstudied in the individual. Diagnosis of the autoimmune disease is the primary goal so palliative therapy can be started.
