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

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.

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).

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.