Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis

Arthritis Rheum. 2012 Nov;64(11):3522-30. doi: 10.1002/art.34595.


Objective: To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA).

Methods: Study participants included the following: 1) a cohort enriched in subjects with HLA-DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti-citrullinated protein antibody (ACPA; by second-generation anti-cyclic citrullinated peptide antibody enzyme-linked immunosorbent assay [ELISA]) and rheumatoid factor (RF; by nephelometry or ELISA for IgA, IgM, or IgG isotype). Individuals were considered autoantibody positive (n = 113) if they had ≥1 RA-related autoantibody; individuals were further categorized as high risk (n = 38) if they had ACPA or positive findings ≥2 assays for RF. Autoantibody-negative individuals (n = 171) served as a comparator group. Antibody to P gingivalis, P intermedia, and F nucleatum were measured. Associations of bacterial antibodies with group status were examined using logistic regression.

Results: Anti-P gingivalis concentrations were higher in high-risk (P = 0.011) and autoantibody positive group (P = 0.010) than in the autoantibody negative group. There were no group differences in anti-P intermedia or anti-F nucleatum concentrations. After multivariable adjustment, anti-P gingivalis concentrations (but not anti-P intermedia or anti-F nucleatum) were significantly associated with autoantibody-positive and high-risk status (P < 0.05).

Conclusion: Immunity to P gingivalis, but not P intermedia or F nucleatum, is significantly associated with the presence of RA-related autoantibodies in individuals at risk of RA. These results support the hypothesis that infection with P gingivalis may play a central role in the early loss of tolerance to self antigens that occurs in the pathogenesis of RA.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bacterial / blood*
  • Arthritis, Rheumatoid / epidemiology*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / microbiology
  • Autoantibodies / blood*
  • Bacteroidaceae Infections / epidemiology*
  • Bacteroidaceae Infections / immunology
  • Cohort Studies
  • Family
  • Female
  • Humans
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Periodontitis / epidemiology*
  • Periodontitis / immunology
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / immunology*
  • Risk Factors
  • Seroepidemiologic Studies


  • Antibodies, Bacterial
  • Autoantibodies