and Polymorphisms Influence Higher Disease Activity in Rheumatoid Arthritis.

BACKGROUND

The activation of NLRP3-inflammasome may contribute to inflammatory processes in rheumatoid arthritis (RA). Functional polymorphisms in the genes coding for its components NLRP3 and CARD8 were associated with a proinflammatory phenotype. Our aim was to investigate the influence of these polymorphisms on RA susceptibility and disease activity at the time of diagnosis and after six months of treatment.

METHODS

A group of 128 RA patients treated with methotrexate and 122 healthy controls were genotyped for rs35829419 (p. Q705K) and rs2043211 (p. C10X) polymorphisms.

RESULTS

RA susceptibility was not influenced by the investigated polymorphisms or their interaction. The investigated polymorphisms explained 8% of variability in DAS28 at the time of diagnosis. Carriers of rs35829419 or rs2043211 polymorphisms had significantly higher DAS28 at the time of diagnosis (p=0.003; p=0.022; respectively). Polymorphic rs2043211 TT genotype was also associated with higher DAS28 after six months of treatment (p=0.033).

CONCLUSIONS

Genetic variability of inflammasome components may contribute to higher disease activity at the time of diagnosis and after 6 months of methotrexate treatment in RA patients. Better understanding of the immunological mechanisms behind a more active course of RA may suggest novel treatment approaches in a subset of patients with a proinflammatory phenotype.