Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population

Objectives: An elevated interleukin (IL)-1 beta response in peripheral blood mononuclear cells (PBMCs) has been observed in systemic juvenile idiopathic arthritis (sJIA), suggesting a role for inflammasomes in the pathogenesis of JIA. We aimed to determine whether genetic polymorphisms of the NLRP3 inflammasome components confer risk for oligoarticular and polyarticular JIA in a Taiwanese population. Method: A total of 118 JIA patients and 103 healthy controls were genotyped for rs4353135 OR2B11/NLRP3 and rs2043211 CARD8 polymorphisms. Clinical laboratory data and serum IL-1 beta of HA patients were evaluated by medical chart review and enzyme-linked immunosorbent assay (ELISA), respectively. The production of IL-17 in lymphocytes of different genotype carriers was measured using flow cytometry. Results: The variant rs4353135 G allele carrier conferred increased risk for oligoarticular and polyarticular JIA. The G allele was also found to be associated with higher levels of clinical inflammatory markers. Moreover, G variant carriers enhanced the lymphocyte IL-17 response. The GIG genotype further increased the need for treatment with the tumour necrosis factor (TNF) inhibitor etanercept. Conclusions: Our data indicate that the rs4353135 OR2B11/NLRP3 polymorphism might be functional in, and could contribute to, the pathophysiology of oligoarticular and polyarticular HA in a Taiwanese population.