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The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?
  1. Paola de Pablo1,
  2. Thomas Dietrich2,
  3. Iain L C Chapple3,
  4. Michael Milward3,
  5. Muslima Chowdhury4,
  6. Peter J Charles4,
  7. Christopher D Buckley1,
  8. Patrick J Venables4
  1. 1Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
  2. 2Department of Oral Surgery, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
  3. 3Department of Periodontology, School of Dentistry, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK
  4. 4Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute for Rheumatology, University of Oxford, Oxford, UK
  1. Correspondence to Dr Paola de Pablo, Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, UK; p.depablo{at}bham.ac.uk

Abstract

Background Studies suggest that periodontitis may be a risk factor for rheumatoid arthritis (RA). The purpose of this study was to determine whether periodontitis is associated with autoantibodies characteristic of RA.

Methods Serum samples were tested for anti-cyclic citrullinated peptide (CCP), anti-mutated citrullinated vimentin (MCV), anti-citrullinated α-enolase peptide-1 (CEP-1), anti-citrullinated vimentin (cit-vim), anti-citrullinated fibrinogen (cit-fib) and their uncitrullinated forms anti-CParg (negative control for anti-CCP), anti-arginine-containing α-enolase peptide-1 (REP-1), anti-vimentin and anti-fibrinogen antibodies in patients with and without periodontitis, none of whom had RA.

Results Periodontitis, compared with non-periodontitis, was associated with a normal frequency of anti-CCP and anti-MCV (∼1%) but a higher frequency of positive anti-CEP-1 (12% vs 3%; p=0.02) and its uncitrullinated form anti-REP-1 (6% vs 2%; p<0.001). Positive antibodies against uncitrullinated fibrinogen and CParg were also more common among those with periodontitis compared to non-periodontitis patients (26% vs 3%; p<0.001, and 9% vs 3%; p=0.06). After adjusting for confounders, patients with periodontitis had 43% (p=0.03), 71% (p=0.002) and 114% (p<0.001) higher anti-CEP-1, anti-REP-1 and anti-fibrinogen titres, compared with non-periodontitis. Non-smokers with periodontitis, compared with non-periodontitis, had significantly higher titres of anti-CEP-1 (103%, p<0.001), anti-REP-1 (91%, p=0.001), anti-vimentin (87%, p=0.002), and anti-fibrinogen (124%, p<0.001), independent of confounders, confirming that the autoantibody response in periodontitis was not due to smoking.

Conclusions We have shown that the antibody response in periodontitis is predominantly directed to the uncitrullinated peptides of the RA autoantigens examined in this study. We propose that this loss of tolerance could then lead to epitope spreading to citrullinated epitopes as the autoimmune response in periodontitis evolves into that of presymptomatic RA.

  • Ant-CCP
  • Autoantibodies
  • Autoimmunity
  • Rheumatoid Arthritis
  • Smoking

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