An increased prevalence of periodontal disease and Porphyromonas gingivalis in anti-CCP positive individuals at-risk of rheumatoid arthritis: a target for prevention?

Importance: The prevalence of periodontitis is increased in rheumatoid arthritis (RA) and the periodontopathic bacteria Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans can citrullinate proteins. Periodontal disease may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA-autoimmunity who have not developed arthritis. Objective: To examine the prevalence of periodontal disease and the abundance of periodontopathic bacteria in anti-cyclic citrullinated protein (anti-CCP) antibody positive at-risk individuals without arthritis. Design: Observational study between 2015 - 2017. Setting: Single-centre, teaching hospital Participants: 48 anti-CCP positive individuals without arthritis (CCP+ at- risk) recruited from a national cohort. 26 early RA (ERA) patients and 32 healthy controls (HC) recruited locally. Interventions/Exposures: Comprehensive periodontal assessment and ultrasound (US) examination of the joints. Main outcome(s) and measure(s): Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area (PISA) in CCP+ at-risk compared with ERA and HC matched for age and smoking. DNA from subgingival plaque from diseased and healthy periodontal sites paired-end sequenced (Illumina HiSeq3000), profiled using MG-RAST and analysed using DESeq2. Mann-Whitney U tests used to compare groups, Spearman Rho for correlations. Wald test allowed comparisons of bacterial abundances. Results: 46/48 (96%) CCP+ at-risk had no US joint inflammation. 73% CCP+ at-risk, 38% HC (p=0.02) and 54% RA had clinical periodontitis. The percentage of periodontal sites (median, IQR) with periodontal disease (PDD) was greater in CCP+ at-risk compared with HC [3.3 (0, 11.3) vs 0 (0, 0.7), p<0.05] and similar to ERA. Median (IQR) PISA (mm2) was higher in CCP+ at-risk compared with HC [221 (81-504) vs 40 (12-205), p=0.0016]. CCP+ at-risk had increased relative abundance of P. gingivalis (but not A. actinomycetemcomitans) at healthy periodontal sites compared with HC [effect size = 3.00, p<0.001] and ERA [effect size = 2.14, p