Pos1425 antibodies to Porphyromonas Gingivalis Associate With the Presence of Rheumatoid Arthritis-Related Autoantibodies in Patients With Periodontitis

Abstract

Background:Epidemiologic studies have demonstrated a link between periodontitis (PD) and rheumatoid arthritis (RA), specifically RA characterized by anti-citrullinated protein antibodies (ACPA). The keystone pathogen driving PD, Porphyromonas gingivalis (Pg), is the only pathogen known to express peptidylarginine deiminase (PAD), a citrullinating enzyme. Hence, Pg has been proposed to be involved in triggering the ACPA response, by generating citrullinated antigens in an inflammatory milieu(1). Another major virulence factor of Pg is arginine gingipain B (RgpB), a proteinase which cleaves proteins so that P.PAD can access the site where citrullination takes place. We have previously shown elevated anti-RgpB IgG levels in ACPA+ RA patients, even before clinical onset(2, 3), and we hypothesize that anti-RgpB IgG could serve as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.Objectives:Based on this hypothesis, we set out to investigate whether anti-RgpB IgG was associated with PD, PD severity, autoimmunity in general, and the ACPA response in particular.Methods:Anti-RgpB IgG, as well as RA- and systemic lupus erythematosus (SLE)-related autoantibodies targeting cyclic citrullinated peptide(s) (CCP2), rheumatoid factor (RF), dsDNA, cardiolipin, and β2 glycoprotein, were measured by ELISA in serum samples from the ParoKrank study, which is a well-characterized cohort of 805 patients with a first myocardial infarction and 805 matched controls, where periodontal status has been determined by dentists(4). In this study, individuals with PD (n=941) were compared to individuals without PD (n=557).Results:We detected significantly elevated (p<0,0001) anti-RgpB IgG levels in PD compared to non-PD individuals, with highest levels recorded in severe PD. Anti-RgpB IgG levels were significantly increased in PD patients positive for CCP2 and/or RF (n=50), when compared to PD patients negative for CCP2 and RF (n=507), p<0,05, and when compared to non-PD individuals positive for CCP2 and/or RF (n=62), p < 0,05. Notably, these differences were not seen for SLE-related autoantibodies. In addition, anti-RgpB IgG levels were significantly elevated amongst MI patients versus controls (p < 0,05), supporting the previous finding that PD is more common among MI patients(4).Conclusion:Our data demonstrates a specific association between severe PD, elevated anti-RgpB IgG levels and RA-related autoantibodies, supporting a role for Pg in linking PD to ACPA+ RA. Further investigation will be needed to confirm whether anti-RgpB IgG can be used as a serological marker to identify PD patients with increased risk of developing ACPA+ RA.References:[1]Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G. Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2004;28(6):311-8.[2]Kharlamova N, Jiang X, Sherina N, Potempa B, Israelsson L, Quirke AM, et al. Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. Arthritis Rheumatol. 2016;68(3):604-13.[3]Johansson L, Sherina N, Kharlamova N, Potempa B, Larsson B, Israelsson L, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther. 2016;18(1):201.[4]Rydén L, Buhlin K, Ekstrand E, Faire Ud, Gustafsson A, Holmer J, et al. Periodontitis Increases the Risk of a First Myocardial Infarction. Circulation. 2016;133(6):576-83.Disclosure of Interests:None declared

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases

“…Besides, another recent research had linked PD to the Alzheimer's disease (AD), remarking that AD patients possessed significantly more plaques and fewer number of teeth as compared to the control group with no AD (de Oliveira Araujo et al, 2020). In accordance with keystone-pathogen hypothesis, P. gingivalis is considered the main pathogen that instigated the progression of these diseases (De Vries et al, 2021).…”