Anti-Porphyromonas gingivalis antibodies titres are associated with non-smoking status in early rheumatoid arthritis: Results from the ESPOIR cohort

250 words) Objectives To investigate the possible link between Porphyromonas gingivalis (P. gingivalis) infection and RA, according to antibody profile, genetic and environmental factors, and RA severity. Patients and Methods For assessing P. gingivalis infection, serum levels of antibodies directed against P. gingivalis LPS were measured in 694 early-RA patients not exposed to steroid or DMARD. Anti-P. gingivalis antibodies titers were compared between early-RA patients and various control groups, and according to various patients characteristics. Results The titre of anti-P. gingivalis antibodies did not significantly differ between RA and controls. Anti-P. gingivalis antibody titres did not significantly differ with ACPA, RF, or HLA-shared epitope status. Anti-P. gingivalis antibody titres were significantly higher among never smoker patients compared to ever-smoker (p= 0.0049). Among non-smokers, high anti-P. gingivalis antibody levels were associated with an higher prevalence of erosive change (mSHS erosion subscale ≥1 : 47.5 vs. 33.3%, p=0.0135). Conclusion In this large early-RA cohort, we did not detect any association of anti-P. gingivalis antibodies with RA or with ACPA status. These results suggest that the association of periodontitis and RA could be linked to other bacterial species than P. gingivalis or to another mechanism than citrullination. Nevertheless we found higher anti-P. gingivalis antibody titres in non-smokers. In addition, in this population of non-smokers, high anti-P. gingivalis antibody titres were associated with a more severe disease. We hypothesize that the role of tobacco in RA pathogenesis is so high that the effect of P. gingivalis could be revealed only in a population not exposed to tobacco. Rheumatoid arthritis (RA) is a systemic, inflammatory autoimmune disorder of unknown, complex and multifactorial aetiology. Its pathophysiology relies on an interaction between gene and environment that triggers auto-immunity. One of the most striking examples is the interaction between tobacco and shared epitope carrying in anti-citrillinated peptide antibody (ACPA) positive RA [1]. In this model, tobacco acts as an external agent inducing citrullination of proteins in the lung that triggers auto-immunity and ACPA production in genetically predisposed subjects, leading to emergence of RA. Among the other potential environmental factors triggering auto-immunity is the oral microbiome. Several epidemiological studies have suggested a link between periodontal disease and RA. The prevalence of periodontal disease is two-fold increased among patients with RA compared to the general population[2-4], and even more in non-smoking RA patients with a 4-fold increased prevalence[5]. In addition, several cohorts have shown that the risk of development of RA was increased in subjects with periodontal disease [6-8]. This risk was even more important in non-smokers [4, 8]. One of the main bacteria implicated in chronic periodontal disease is Porphyromas (P) gingivalis [9], a microorganism of the oral cavity located in the sub-gingival tissue. P. gingivalis has been incriminated in RA pathogenesis because it is one of the few microorganisms with a deiminase capable of transforming arginine into citrulline, and is thus suspected of playing a possible role in the production of ACPA. Some recent studies suggest that the presence of P. gingivalis could be associated with development of RA [10-13] and particularly ACPA-positive RA [10, 11, 13-15]. Nevertheless, these results remain controversial [4, 16] and were obtained for most of them from small cohorts. The objective of this study was to investigate the relationship between P. gingivalis infection (as measured by serum levels of anti-P. gingivalis antibodies) and RA. This study also aimed to investigate the possible link between P. gingivalis infection and RA antibody profile (principally ACPA status), genetic and environmental factors and structural damage in a large cohort of early arthritis patients. PATIENTS AND METHODS