Immunity to citrullinated proteins in rheumatoid arthritis

Annu Rev Immunol. 2008;26:651-75. doi: 10.1146/annurev.immunol.26.021607.090244.

Abstract

Antibodies to citrullinated proteins (ACPA), i.e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA). Studies on anticitrulline immunity, summarized in this review, demonstrate that the criterion-based syndrome RA should be subdivided into at least two distinct subsets (ACPA-positive and ACPA-negative disease). A new etiological model is proposed for ACPA-positive RA, built on MHC class II-dependent activation of adaptive immunity. Fundamentals of this model include the following: (a) ACPA antedate onset of arthritis; (b) ACPA may aggravate arthritis in rodents; (c) ACPA are triggered in the context of genes that confer susceptibility to RA (HLA-DRB1 SE) and by environmental agents triggering RA (smoking or bacterial stimuli); (d) ACPA may complex with citrullinated proteins present in target tissue as part of a multistep process for arthritis development. The model provides a new basis for molecular studies on the pathogenesis of ACPA-positive arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Citrulline / immunology*
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • HLA-DRB1 Chains
  • Humans
  • Protein Processing, Post-Translational / immunology
  • Proteins / immunology*
  • Proteins / metabolism

Substances

  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Proteins
  • Citrulline