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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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
Article number152176
JournalSeminars in Arthritis and Rheumatism
StatePublished - Apr 2023
Externally publishedYes


  • ACPA
  • Periodontitis
  • Porphyromonas gingivalis
  • Prevotella intermedia
  • Rheumatoid arthritis
  • Rheumatoid factor


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