Drugs and autoimmunity - A contemporary review and mechanistic approach

Christopher Chang, M. Eric Gershwin

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalJournal of Autoimmunity
Volume34
Issue number3
DOIs
StatePublished - May 2010

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Keywords

  • Adverse drug reactions
  • Autoantibodies
  • Autoimmunity
  • DNA hypomethylation
  • Drug reactions
  • Drug-induced lupus
  • Drugs
  • Immune tolerance
  • Lupus
  • Medications
  • Tolerance
  • Tumor-necrosis factor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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