Serum antibodies to periodontal pathogens prior to rheumatoid arthritis diagnosis: A case-control study

Joyce A Lee, Ted R Mikuls, Kevin D Deane, Harlan R Sayles, Geoffrey M Thiele, Jess D Edison, Brandie D Wagner, Marie L Feser, Laura K Moss, Lindsay B Kelmenson, William H Robinson, Jeffrey B Payne

Research output: Contribution to journalArticlepeer-review


OBJECTIVES: 1) To quantify the association between anti-Porphyromonas gingivalis serum antibody concentrations and the risk of developing rheumatoid arthritis (RA), and 2) to quantify the associations among RA cases between anti-P. gingivalis serum antibody concentrations and RA-specific autoantibodies. Additional anti-bacterial antibodies evaluated included anti-Fusobacterium nucleatum and anti-Prevotella intermedia.

METHODS: Serum samples were acquired pre- and post- RA diagnosis from the U.S. Department of Defense Serum Repository (n = 214 cases, 210 matched controls). Using separate mixed-models, the timing of elevations of anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations relative to RA diagnosis were compared in RA cases versus controls. Associations were determined between serum anti-CCP2, ACPA fine specificities (vimentin, histone, and alpha-enolase), and IgA, IgG, and IgM RF in pre-RA diagnosis samples and anti-bacterial antibodies using mixed-effects linear regression models.

RESULTS: No compelling evidence of case-control divergence in serum anti-P. gingivalis, anti-F. nucleatum, and anti-P. intermedia was observed. Among RA cases, including all pre-diagnosis serum samples, anti-P. intermedia was significantly positively associated with anti-CCP2, ACPA fine specificities targeting vimentin, histone, alpha-enolase, and IgA RF (p<0.001), IgG RF (p = 0.049), and IgM RF (p = 0.004), while anti-P. gingivalis and anti-F. nucleatum were not.

CONCLUSIONS: No longitudinal elevations of anti-bacterial serum antibody concentrations were observed in RA patients prior to RA diagnosis compared to controls. However, anti-P. intermedia displayed significant associations with RA autoantibody concentrations prior to RA diagnosis, suggesting a potential role of this organism in progression towards clinically-detectable RA.

Original languageEnglish
Pages (from-to)152176
JournalSeminars in Arthritis and Rheumatism
StatePublished - Apr 2023


  • Humans
  • Vimentin
  • Histones
  • Case-Control Studies
  • Arthritis, Rheumatoid
  • Autoantibodies
  • Antibodies, Bacterial
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulin A
  • Phosphopyruvate Hydratase
  • Rheumatoid Factor


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