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We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized. [ABSTRACT FROM AUTHOR]

We compared the prognostic factors and outcome of 30 patients with juvenile chronic arthritis (JCA) extending into adult life with those of 30 patients with adult rheumatoid arthritis (RA) at a university adult rheumatology clinic; pairs were matched for sex and duration of disease (mean 8 years). One-third of JCA patients had seronegative polyarticular disease and another third had oligoarticular disease. In a third of the JCA patients, the clinical presentation changed during the follow-up. Over half of the RA patients had seropositive polyarticular and a one-third had seronegative polyarticular disease. Fewer seropositive patients were recorded in the JCA group than in the RA group both at the beginning (16.7% versus 56.7%; p = 0.003) and at the end of the follow-up (14.3% versus 59.3%; p = 0.001). JCA patients developed less radiographic changes than RA patients (46.7% versus 76.7%; p = 0.034); oligoarthritis in the JCA group had the best prognosis whereas seropositive polyarthritis in the RA group had the worst prognosis. Significantly more patients with JCA than RA (60% versus 23%; p = 0.009) were in remission at the end of the follow-up. In conclusion, when studied in adult life, the long-term prognosis is better in patients with JCA than in those with RA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]