title: The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?
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 (16% 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.
authors: Rheumatology Research Group, School of Immunity & Infection, College of Medical & Dental Sciences, University of Birmingham, , Birmingham, UK.
authors: Paola
authors: P
authors: de Pablo
authors: Thomas
authors: T
authors: Dietrich
authors: Iain L C
authors: IL
authors: Chapple
authors: Michael
authors: M
authors: Milward
authors: Muslima
authors: M
authors: Chowdhury
authors: Peter J
authors: PJ
authors: Charles
authors: Christopher D
authors: CD
authors: Buckley
authors: Patrick J
authors: PJ
authors: Venables
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D002956:Citrulline / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010518:Periodontitis / Q000150:complications / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000276:immunology; D012907:Smoking / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000276:immunology; D014746:Vimentin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010456:Peptides, Cyclic; D025521:Tumor Suppressor Proteins; D014746:Vimentin; C487763:cyclic citrullinated peptide; D002956:Citrulline; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: Ant-CCP; Autoantibodies; Autoimmunity; Rheumatoid Arthritis; Smoking