Association between anti-P. gingivalis antibodies and anti-citrullinated vimentin antibodies in the patients with rheumatoid arthritis.

Abstract

Abstract Objectives Anti-citrullinated-protein auto-antibodies (ACPA), especially that react to citrullinated vimentin (CV), are implicated in the pathogenesis of Rheumatoid arthritis (RA). P. gingivalis (Pg), a key pathogen of periodontitis, can citrullinate the host proteins by production of Pg-derived peptidylarginine deiminase (PPAD). This study evaluated the relationship among antibodies (Abs) that react cyclic citrullinated protein (CCP), CV and periodontal pathogens in the serum of RA patients or control subjects. Methods Blood serum of healthy subjects (n=10) and RA patients (n=26) were obtained from Precision for Medicine. Six distinctive peptide sequences of Vimentin (#1–#6) and corresponding CV (#1’–#6’) peptides were synthesized. ELISA was employed to detect IgG Ab titers for CCP, intact vimentin and CV peptides. Fixed periodontal pathogens, Pg 33277, F. nucleatum, P. intermedia, A. actinomycetemcomitans (Aa) Y4, S. mitis, S. gordonii, A. odontolyticus, and C. gingivalis were also used as IgG ELISA antigens. Results The levels of anti-CCP Ab were higher in RA patients with anti-Pg Ab than those without anti-Pg Ab. Since elevated anti-Pg Ab is hallmark of periodontitis, it is conceivable that RA patients with anti-Pg Ab would have periodontitis. However, there was no association between anti-CCP Ab and the Abs reactive to the other bacteria. Very interestingly, RA patients with anti-Pg Ab, but not those without anti-Pg Ab, showed significantly elevated Ab response to #6’ CV peptide compared to intact #6 vimentin peptide, among six peptide sequences tested. Conclusions Our findings indicated that periodontitis may be associated with the induction of ACPA via PPAD-mediated citrullination of host proteins. Supported by NIH NIDCR grants, DE-027851, DE-028715 and DE-331851