Association between shared epitope and anti-citrullinated peptide antibodies in rheumatoid arthritis: A systematic review and meta-analysis

The group of major histocompatibility complex (MHC) alleles known as shared epitope (SE) is to date the strongest rheumatoid arthritis (RA) genetic risk factor. Many studies have shown that the measurement of anti-citrullinated peptides antibodies would be useful in the diagnosis and follow-up of RA.

Our aim is to determine the magnitude of the association between the possession of SE alleles and serum positive titres of antibodies against citrullinated peptides.

Our selection criteria included case–control or cohort studies, where data involving antibodies against citrullinated peptides and SE in RA patients were available. No date or language restrictions were imposed.

Bibliographical databases MEDLINE, Cochrane Database of Systematic Reviews and EMBASE were searched for pertinent literature. Two reviewers independently identified relevant citations and extracted data. Data extraction was then checked by two different reviewers.

Five published and one unpublished (own data) studies were included in the final meta-analysis. Overall, 2700 European descent RA patients were included in this meta-analysis. A significant association between SE and positive titres of serum antibodies against citrullinated peptides [OR(95% CI) = 3.19 (2.21–4.60)] was found.

Positive titres for antibodies against citrullinated peptides are threefold more frequent in RA patients who carry SE alleles than in those patients lacking them.