Somatic mutations contribute to tumorigenesis. Although these mutations occur in all proliferating cells, their accumulation under non-malignant conditions, such as in autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; in 20% (5/25) of patients CD8+ T cells, but not CD4+ T cells, harbour somatic mutations. In healthy controls (n=20), only one mutation is identified in the CD8+ T-cell pool. Mutations exist exclusively in the expanded CD8+ effector-memory subset, persist during follow-up, and are predicted to change protein functions. Some of the mutated genes (SLAMF6, IRF1) have previously been associated with autoimmunity. RNA sequencing of mutation-harbouring cells shows signatures corresponding to cell proliferation. Our data provide evidence of accumulation of somatic mutations in expanded CD8+ T cells, which may have pathogenic significance for RA and other autoimmune diseases.

ObjectivesTo investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health.DesignProspective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once.Settings and participantsThe study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants.Outcome measuresDegree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria.ResultsModerate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results.ConclusionsModerate periodontitis was more frequent in patients with RA than in controls. Patients with ERA and CRA exhibited poorer periodontal health parameters when compared with controls. There was no association between antirheumatic treatment and periodontal parameters.

The study hypothesis was confirmed by showing that the patients with rheumatic diseases reported oral discomfort and reduced quality of life more often when compared with controls.

Elevated serum concentrations of MMP-8 and IL-6 in CRA patients reflected chronic RA, while elevated salivary concentrations of MMP-8 levels in ERA patients reflected increased periodontal inflammation. Key messages Concentrations of inflammatory biomarkers in serum and saliva were different between patients with RA and healthy controls. Concentrations of MMP-8 and of IL-6 in serum were elevated in patients with chronic RA reflecting joint inflammation and the burden of established RA. Concentrations of MMP-8 in saliva was elevated already at the early stage of RA and the level of salivary MMP-8 was associated with poor periodontal health both in patients with early and in those with chronic RA.