Objectives CARD8 and NLRP3 are constituents of the inflammasome which regulates interleukin 1β production. The influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity were evaluated.
Methods CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in >500 controls and patients with early RA from northern Sweden. The patients were monitored regularly over a 2–year period. The 28-joint disease activity score (DAS28) and its separate components were compared across genotypes.
Results Patients with one or more variant alleles in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2-year follow-up period despite receiving disease-modifying antirheumatic drugs to a greater extent. CARD8-X was significantly over-represented among patients who received anti-tumour necrosis factor therapy during the first 2 years. CARD8 and NLRP3 genotypes did not influence radiological joint damage and were not associated with an increased susceptibility.
Conclusions Carriage of CARD8-X is associated with a worse disease course in early RA.
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Funding This study was supported by grants from Swedish Research Council (K2007-52X-20307-01-3), King Gustaf V’s 80-Year Fund, the Swedish Rheumatism Association, the Nanna Svartz Foundation, the Tore Nilson Foundation, the Medical Research Council of Southeast Sweden (FORSS-6622), the County Council of Östergötland and the Medical Faculty of Umeå University, Umeå, Sweden.
Competing interests None.
Ethics approval The regional ethics committee at the University Hospital at Umeå approved the study protocol and all participants gave their written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.