The reason our immune system malfunctions is not completely understood. Research has found an association between the presence of certain human leukocyte antigen (HLA) types and increased risk of the development of a specific autoimmune disorder. One current hypothesis is that the following series of events occurs, resulting in the initiation of an autoimmune reaction.
Step one: 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. For example, in systemic lupus erythematosus (SLE), the female-to-male ratio is 9:1. 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. 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.
Step two: Triggering event
The second step is the occurrence of a triggering event that leads to a break in 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 silicon 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.
Step three: Development of autoantibodies
The third step is the development of autoantibodies and the subsequent 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.
