title: Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology.
abstract: OBJECTIVE
  To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles in patients with periodontitis, patients with RA, and controls.
  
  
  METHODS
  Anti-RgpB IgG was measured by enzyme-linked immunosorbent assay in 65 periodontitis patients and 59 controls without periodontitis, and in 1,974 RA patients and 377 controls without RA from the Swedish population-based case-control Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Autoantibody status, smoking habits, and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using the Mann-Whitney U test. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs) for the association of anti-RgpB IgG with different subsets of RA patients.
  
  
  RESULTS
  Anti-RgpB antibody levels were significantly elevated in periodontitis patients compared to controls without periodontitis, in RA patients compared to controls without RA, and in ACPA-positive RA patients compared to ACPA-negative RA patients. There was a significant association between anti-RgpB IgG and RA (OR 2.96 [95% CI 2.00, 4.37]), which was even stronger than the association between smoking and RA (OR 1.37 [95% CI 1.07, 1.74]), and in ACPA-positive RA there were interactions between anti-RgpB antibodies and both smoking and the HLA-DRB1 SE.
  
  
  CONCLUSIONS
  Our study suggests that the previously reported link between periodontitis and RA could be accounted for by P gingivalis infection, and we conclude that P gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RA patients.
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nastya
authors.initials: N
authors.lastname: Kharlamova
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sherina
authors.affiliation: University of Louisville School of Dentistry, Louisville, Kentucky.
authors.forename: Barbara
authors.initials: B
authors.lastname: Potempa
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Israelsson
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, and University of Oxford, Oxford, UK.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Quirke
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kaja
authors.initials: K
authors.lastname: Eriksson
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tülay
authors.initials: T
authors.lastname: Yucel-Lindberg
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, and University of Oxford, Oxford, UK.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Venables
authors.affiliation: University of Louisville School of Dentistry, Louisville, Kentucky, and Jagiellonian University, Krakow, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.affiliation: Karolinska Institutet and Centre for Occupational and Environmental Medicine at Stockholm County Council, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Lundberg
mesh_terms: D000907:Antibodies, Bacterial / Q000032:analysis*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000209:etiology*; D016866:Bacteroidaceae Infections / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D010518:Periodontitis / Q000150:complications / Q000276:immunology*; D011110:Polymorphism, Genetic; D016966:Porphyromonas gingivalis / Q000276:immunology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012907:Smoking / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D037521:Virulence Factors; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22