Autoimmune Disorders

In autoimmune disorders, the immune system produces antibodies to an endogenous antigen (autoantigen). The following hypersensitivity reactions may be involved:

• Type II: Antibody-coated cells, like any similarly coated foreign particle, activate the complement system, resulting in tissue injury.
• Type III: The mechanism of injury involves deposition of antibody-antigen complexes.
• Type IV: Injury is T-cell-mediated.

(See also Overview of Allergic and Atopic Disorders.)

For specific autoimmune disorders, see elsewhere in THE MANUAL.

Women are affected more often than men.

Etiology of Autoimmune Disorders

Mechanisms

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:

• Chemical: Certain chemicals can bind with body proteins, making them immunogenic, as occurs in some cases of drug-induced immune hemolytic anemia.
• Physical: For example, ultraviolet light induces keratinocyte apoptosis and subsequent altered immunogenicity of autoantigens, resulting in photosensitivity, as can occur in cutaneous lupus erythematosus.
• Biologic: For example, in animal models, persistent infection with an RNA virus that combines with host tissues alters autoantigens biologically, resulting in an autoimmune disorder resembling systemic lupus erythematosus (SLE).

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.