Merck Manual

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Autoimmune Disorders


James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Reviewed/Revised Oct 2022

Specific autoimmune disorders in THE MANUAL include the following:

Women are affected more often than men.

Etiology of Autoimmune Disorders


Several mechanisms may account for the body’s attack on itself:

  • Autoantigens may become immunogenic if they are altered in some way.

  • Antibodies to a foreign antigen may cross-react with an unaltered autoantigen (eg, antibodies to streptococcal M protein may cross-react with human heart muscle).

  • Autoantigens 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:

Genetic factors

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. If one twin has an autoimmune disorder, the other twin is more likely to have it if they are identical rather than fraternal twins.

Most autoimmune disorders have a polygenic etiology, and allelic variants within the HLA-gene locus nearly always contribute.

Defense mechanisms

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.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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