title: Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.
abstract: BACKGROUND
  Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated.
  
  
  METHODS
  The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was <5.
  
  
  RESULTS
  Two patients with GAgP (3.9%), no patient with GChP and two controls (2.2%, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1%, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3%) than no carriers (0.7 and 0%, pFisher 0.053).
  
  
  CONCLUSIONS
  GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti-CEP-1 autoantibodies. The putative relationship between periodontitis and RA should be investigated in further studies.
authors: Department of Operative Dentistry and Periodontology, Martin-Luther University Halle-Wittenberg, Große Steinstrasse 19, 06108, Halle (Saale), Germany. stefan.reichert@uk-halle.de.
authors: Stefan
authors: S
authors: Reichert
authors: EUROIMMUN AG, Lubeck, Germany. w.schlumberger@euroimmun.de.
authors: Wolfgang
authors: W
authors: Schlumberger
authors: EUROIMMUN AG, Lubeck, Germany. c.daehnrich@euroimmun.de.
authors: Cornelia
authors: C
authors: Dähnrich
authors: EUROIMMUN AG, Lubeck, Germany. n.hornig@euroimmun.de.
authors: Nora
authors: N
authors: Hornig
authors: HLA Laboratory (Ghatt), Martin-Luther University Halle-Wittenberg, Halle, Germany. hla-labor@uk-halle.de.
authors: Wolfgang
authors: W
authors: Altermann
authors: Department of Operative Dentistry and Periodontology, Martin-Luther University Halle-Wittenberg, Große Steinstrasse 19, 06108, Halle (Saale), Germany. hans-guenter.schaller@uk-halle.de.
authors: Hans-Günter
authors: HG
authors: Schaller
authors: Department of Operative Dentistry and Periodontology, Martin-Luther University Halle-Wittenberg, Große Steinstrasse 19, 06108, Halle (Saale), Germany. susanne.schulz@medizin.uni-halle.de.
authors: Susanne
authors: S
authors: Schulz
mesh_terms: D000328:Adult; D010520:Aggressive Periodontitis / Q000150:complications / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000150:complications / Q000276:immunology*; D004247:DNA / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000276:immunology; D010751:Phosphopyruvate Hydratase / Q000737:chemistry* / Q000276:immunology; D016133:Polymerase Chain Reaction; D016966:Porphyromonas gingivalis; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D004247:DNA; D010751:Phosphopyruvate Hydratase