The anti-citrullinated antibody repertoire in periodontitis: a role in the induction of autoimmunity in rheumatoid arthritis?

Abstract

BackgroundData suggest that periodontal disease (periodontitis) may be a risk factor for rheumatoid arthritis. Anti-citrullinated peptide/protein antibodies (ACPA) are highly specific for rheumatoid arthritis, and epitope spreading arises years before clinical onset of the disease. The purpose of this study was to determine the immune reactivity to ACPA and their uncitrullinated control peptides in patients with periodontitis. MethodsACPA serology was determined in patients with and without periodontitis, including anti-cyclic citrullinated peptide antibodies (anti-CCP), anti-mutated citrullinated vimentin antibodies (anti-MCV), and antibodies with specificity for different citrullinated peptides, including enolase (CEP-1), vimentin (cit-vim), fibrinogen (cit-fib), and their uncitrullinated forms (REP-1, vim, and fib, respectively). FindingsWe included 96 patients with and 98 without periodontitis, none of whom had rheumatoid arthritis at inclusion. Compared with patients without periodontitis, patients with the disease had a higher frequency of antibodies against CEP-1 (3% [3/98] vs 12% [12/96], p=0·02) and REP-1 (2% [2/98] vs 6% [6/96], p<0·001). Antibodies against fib (negative control peptide for cit-fib) and cparg (negative control peptide for CCP) were also more common among those with periodontitis than in those without (26% [25/96] vs 3% [3/98], p<0·001; and 9% [9/96] vs 3% [3/98], p=0·06, respectively). 79 (49%) of 149 non-smokers with periodontitis had significantly higher titres of antibodies against CEP-1 (103% difference in titres, p<0·001), REP-1 (91%, p=0·001), vimentin (87%, p=0·002), and fib (124%, p<0·001), than did patients without periodontitis, independent of age and sex. InterpretationIn patients without rheumatoid arthritis, periodontitis is associated with higher titres of antibodies to both citrullinated and uncitrullinated peptides in non-smokers suggesting that periodontitis may contribute to the development of autoimmunity related to rheumatoid arthritis. FundingGums & Joints Collaborative EU Framework Programme 7 project and Birmingham and Black Country Comprehensive Local Research Network.