Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis

Objective: Prevotella copri (Pc), a gut commensal, has been reported to be an immune relevant organism in individuals with rheumatoid arthritis (RA). Our goal was to evaluate anti-Pc antibody responses in our participant cohorts and determine when in the natural history of RA such responses develop. Methods: Serum levels of IgA and IgG anti-Pc-p27, an immunogenic Pc protein, were analyzed in study participants at-risk for the development of RA, those who transitioned to RA, in those with early RA (< one year of disease), and in those with established RA, compared to matched controls. Additionally, levels of anti-Pc-p27 antibodies were evaluated in individuals stratified by RA-related autoantibody status. Results: Overall, participants with RA had significantly higher levels of IgA anti-Pc-p27 antibodies and trends towards higher levels of IgG anti-Pc-p27 antibodies when compared to their matched controls. When stratified by early versus established RA, early RA participants had median values of IgG anti-Pc-p27 antibodies that were overall higher, whereas median values of IgA anti-Pc-p27 were statistically significantly higher in participants with established RA, compared with their matched controls. In the autoantibody specific analyses, the at-risk population with anti-CCP antibodies, but not RF, demonstrated trends towards increased levels of IgG anti-Pc-p27. Additionally, RA participants who were CCP+/RF+ had significantly increased levels of IgA anti-Pc-p27 antibodies and a trend toward levels of IgG anti-Pc-p27 antibodies when compared to their matched controls. Conclusion: These findings support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.