Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology

Arthritis Rheumatol. 2016 Mar;68(3):604-13. doi: 10.1002/art.39491.


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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / analysis*
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / analysis
  • Autoimmune Diseases / etiology*
  • Bacteroidaceae Infections / complications*
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Humans
  • Immunoglobulin G / analysis
  • Periodontitis / complications
  • Periodontitis / immunology*
  • Polymorphism, Genetic
  • Porphyromonas gingivalis / immunology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Smoking / immunology*
  • Virulence Factors / immunology


  • Antibodies, Bacterial
  • Autoantibodies
  • Epitopes
  • Immunoglobulin G
  • Virulence Factors
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22