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We have read with great interest the paper from Courbon et al providing the first in vivo demonstration of arthritis induced by oral priming with Porphyromonas gingivalis in rats, though an increased prevalence of periodontal diseases has been observed in rheumatoid arthritis (RA) for a century.1 This major agent of periodontal disease is one of the only bacterium known to express a peptidylarginine deiminase. Citrullinated epitopes, generated by its enzymatic activity, bind to HLA-DRB1*04:01/04 with higher affinity than uncitrullinated epitopes, leading to an enhanced T-cell response 2 and trigger the production of anti-citrullinated protein antibody (ACPA).
Alcohol consumptio is a major risk factor for chronic periodontitis. Interestingly, two articles suggested an association between long-term moderate alcohol drinking and reduced risk of RA onset.3 Moreover, an inverse relationship between moderate alcohol consumption and radiological progression was suggested in men with early RA but not in women in two independent RA patient cohorts.4
Therefore, we investigated relationship between P. gingivalis infection, alcohol consumption, gender and radiological progression in American College of Radiology/European League Against Rheumatism (ACR/EULAR) 2010 early RA patients of the ESPOIR cohort (ethic no 020307).
Patients presented with inflammatory arthritis of at least two swollen joints lasting for 6 weeks to 6 months, who were not exposed to steroids or disease-modifying antirheumatic drugs and fulfilling ACR/EULAR 2010 RA criteria at inclusion were included. P. gingivalis infection was measured at baseline by serum levels of anti-P. gingivalis antibodies.5 Radiological progression was defined as a progression ≥1 point/year of modified Sharp/van der Heijde score within the first 5 years of follow-up.5Smoking status and alcohol consumption were respectively collected as dichotomous and quantitative (in grams/day) variable at all visits up to 5 years as previously described.4
A total of 533 patients with early RA fulfilling 2010 ACR/EULAR criteria were included; 417 (78%) patients were female, mean age was 50 years (online supplementary table 1). A total of 266 (50%) patients were ACPA positive and 282 (53%) were rheumatoid factor (RF) positive; C reactive protein (CRP) was increased in 372 (70%) patients. A total of 93 (18%) patients had erosive RA at baseline, and 409 (77%) patients had radiological progression at 5 years. A total of 133 patients (25%) were seropositive at baseline for P. gingivalis. About 246 (46%) patients were active smokers. About 90 (17%) patients were alcohol consumers. Among them, 30 (6%) patients were considered alcohol abusers (>20 g/day for women and >30 g/day for men).4
We did not observe any difference of baseline demographics characteristics in P. gingivalis seropositive and seronegative patients (table 1). The adjusted OR (table 2) and the multivariate analysis (online supplementary table 1) did not find any significant interaction between P. gingivalis serology, alcohol consumption, gender and radiological progression.
Hence, the beneficial role of alcohol consumption on radiological progression in men with RA 4 was not explained in our study by interaction with P. gingivalis seropositivity. One of the limits of our study is our assay of P. gingivalis infection. Anti-P. gingivalis ELISA is robust for assessing long-term exposure to P. gingivalis but is not associated with current active infection, and its titre is not a reliable proxy of bacterial burden.5 However, our assay showed increased titres of anti-P. ginvivalis antibodies in patients with periodontal disease, who constitute a relevant positive control group.5 Quantitative PCR could be considered for future studies to provide a better evaluation of bacterial activity in periodontal disease associated with RA and possible further opportunity for RA treatment as non-surgical periodontal treatment decreases both P. ginvivalis-related periodontal disease and disease activity of RA.6
The authors thank the Direction de la Recherche Clinique et de l’innovation of CHU Grenoble Alpes for its support. An unrestricted grant from Merck Sharp and Dohme was allocated for the first 5 years. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie, Roche-Chugai also supported the ESPOIR cohort study. The authors also wish to thank Nathalie Rincheval (CHU Montpellier and EA 2415) who did expert monitoring and data management and all the investigators who recruited and followed the patients (F Berenbaum, Paris-Saint Antoine; M C Boissier, Paris-Bobigny; A Cantagrel, Toulouse; B Combe, Montpellier; M Dougados, Paris-Cochin; P Fardelone and P Boumier Amiens; B Fautrel, Paris-La Pitié; R M Flipo, Lille; Ph. Goupille, Tours; F Liote, Paris- Lariboisière; O Vittecoq, Rouen; X Mariette, Paris Bicetre; O Meyer et Ph Dieude, Paris Bichat; A Saraux, Brest; Th Schaeverbeke, Bordeaux; J Sibilia, Strasbourg); V Devauchelle and C Lukas for expert X-ray reading and S Martin (Paris Bichat) who did all the central dosages of CRP, IgA and IgM RF and anti-CCP antibodies. The authors also thank Pr Maurice Dematteis for fruitful comments on our study.
JH and AB contributed equally.
Collaborators Bruno Fautrel and Xavier Mariette.
Contributors JH wrote the manuscrit; interpretated statistical analysis; AB generated statistical analysis and critically reviewed the study proposal; XR served as scientific advisors and critically reviewed the study proposal; BF served as scientific advisors and critically reviewed the study proposal; FS served as scientific advisors and critically reviewed the study proposal; AB generated statistical analysis and critically reviewed the study proposal; PG served as scientific advisors and critically reviewed the study proposal.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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