Drugs and autoimmunity--a contemporary review and mechanistic approach.
Drug-induced autoimmunity is an idiosyncratic, non-IgE immune related drug reaction. Interestingly, although many drugs have been reported to induce autoantibodies, only a few have a definitive association with drug-induced autoimmune disease. The prototype disease is drug-induced lupus and the typical drug for drug-induced lupus is minocycline. The production of autoantibodies and the induction of symptoms in drug-induced lupus results from a variety of mechanisms, which can include suppression of central or peripheral tolerance, alteration of gene transcription in T and B cells, abnormal cytokine and/or cytokine receptor balance and function, chromatin structure modification and antigen modification. Multiple mechanisms may apply for different drugs, and understanding the pharmacological actions of these agents helps us decipher the etiology. For example, DNA hypomethylation may occur with hydralazine, which leads to increased transcription, increased LFA-1, the generation of autoreactive T cells and a breakdown in peripheral tolerance. Frequently, more than one pathway may be involved. Interestingly, most patients with newly formed autoantibodies resulting from drugs do not develop clinical disease. Nonetheless, the explosion in the use of biological modifiers has been associated with production of autoantibodies, an observation that illustrates the complex nature of these interactions, in that these agents are frequently used to treat autoimmunity, yet may produce autoimmune diseases themselves.
Chang
Christopher
C
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA. c3chang@yahoo.com
Gershwin
M Eric
ME
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D019175:DNA Methylation / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
D001323:Autoantibodies; D016207:Cytokines