In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following hypersensitivity reactions may be involved:
For specific autoimmune disorders, see elsewhere in The Manual.
Women are affected more often than men.
Several mechanisms may account for the body's attack on itself. Autoantigens may become immunogenic if they are altered in some way. Alternatively, antibodies to a foreign antigen may cross-react with an unaltered antigen (eg, antibodies to streptococcal M protein may cross-react with human heart muscle). Or antigens normally sequestered from the immune system can become exposed and cause an autoimmune reaction (eg, systemic release of melanin-containing uveal cells after eye trauma triggers sympathetic ophthalmia).
Autoantigens may be altered chemically, physically, or biologically:
Relatives of patients with autoimmune disorders often also have autoantibodies. The specificity of autoantibodies in patients and in their relatives is frequently, but not always, similar. The incidence of autoimmune disorders is higher in identical twins than in fraternal twins.
Most autoimmune disorders have a polygenic etiology, and allelic variants within the HLA-gene locus nearly always contribute.
Normally, potentially pathologic autoimmune reactions are avoided because of the immunologic tolerance mechanisms of clonal deletion and clonal anergy. Any autoreactive lymphocytes not controlled by these mechanisms are usually restrained by Foxp3+ regulatory T cells. A regulatory T-cell defect may interfere with any of these protective mechanisms, resulting in autoimmunity. Anti-idiotype antibodies (antibodies to the antigen-combining site of other antibodies) may interfere with regulation of antibody activity.
Last full review/revision March 2014 by Peter J. Delves, PhD
Content last modified March 2014