期刊
ANNUAL REVIEW OF IMMUNOLOGY
卷 26, 期 -, 页码 651-675出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev.immunol.26.021607.090244
关键词
genes; environment; autoimmunity; smoking; HLA-DR
类别
Antibodies to citrullinated proteins (ACPA), i.e., to peptides post-translationally modified by the conversion of arginine to citrulline, are specific serological markets 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.
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