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

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.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.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.These findings support a potential etiologic role for this microorganism in both RA preclinical evolution and the subsequent pathogenesis of synovitis.