P042/O05 Molecular mimicry and autoimmunity: anti-P.gingivalis antibody response in ACPA-positive rheumatoid arthritis

Career situation of first and presenting author Student for a master or a PhD. Introduction The presence of anti-citrullinated protein antibodies (ACPAs) is a hallmark of rheumatoid arthritis (RA). ACPAs specifically recognize citrullinated epitopes, a result of a post-translational modification catalyzed by peptidyl arginine deiminases (PAD). Based on the unique feature of the periodontal bacteria Porphyromonas gingivalis (P.gingivalis) to express P.PAD it has been suggested that ACPA-positive RA may be precipitated in the gum mucosa. Objectives To address this hypothesis our aims were to investigate the antibody response against a citrullinated P.PAD peptide (CPP3) in patients with RA, chronic periodontitis (PD) and in controls. In addition, we generated monoclonal antibodies (mAbs) from gingival tissue B cells of RA patient aiming to investigate whether citrulline-specific B cells may reside in the gingiva. Methods Gingival tissue-derived single CD19+ B cells from an ACPA-positive RA patient with PD were sorted by flow cytometry. Immunoglobulin variable region genes were sequenced and expressed to generate recombinant mAbs. CPP3-reactivity was analysed by ELISA in serum samples from 66 PD patients, 63 periodontally healthy controls (non-PD), 200 RA patients, and 120 non-RA controls, as well as in 55 mAbs. Differences in antibody levels were examined using Mann-Whitney U test for independent groups. Results Anti-CPP3 antibody levels were low in non-PD controls, while 65% of PD patients showed elevated levels (p Conclusions This study shows that a substantial proportion of systemically healthy individuals possess ACPAs directed against P.gingivalis, and these ACPAs also bind epitopes on human proteins. Based on our data, we propose that the ACPA response may be triggered by P.gingivalis via an antibody response against CPP3, which cross-reacts with human citrullinated proteins by mechanisms of molecular mimicry. Disclosure of Interest None declared.