Objectives: CARD8 and NLRP3 are constituents of the inflammasome, which regulates interleukin 1β production. We evaluated the influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity.
Methods: CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in >500 controls and early RA patients from northern Sweden. The patients were monitored regularly during 2 years. The 28 joint disease activity score (DAS28) and its separate components were compared across genotypes.
Results: Patients with ≥1 variant allele in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2 year follow-up, despite receiving disease-modifying anti-rheumatic drugs to a higher extent. CARD8-X was significantly overrepresented among patients who received anti-TNF therapy during the first two years. CARD8 and NLRP3 genotypes did not influence radiological joint damage or associate with an increased susceptibility.
Conclusions: Carriage of CARD8-X associates with a worse disease course in early RA.