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

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.