Expression and clinical significance of A20 and NLRP3 genes in juvenile idiopathic arthritis

Abstract:

Objective To analyze the expression of A20 and NLRP3 genes in healthy controls（HCs） and those with juvenile idiopathic arthritis（JIA），so as to investigate its role in predicting the efficacy of biological agents in JIA patients.Methods According to the 2001 International League of Associations for Rheumatology（ILAR） diagnostic criteria for juvenile idiopathic arthritis，33 HCs and 68 children newly diagnosed with JIA were enrolled in the study，and their peripheral blood mononuclear cells（PBMCs） were collected. Quantitative real-time PCR（qRT-PCR） was used to detect the mRNA expression of A20 and NLRP3 genes. Inactive disease was regarded as clinical remission（CR） according to the Juvenile Idiopathic Arthritis Disease Activity Score proposed by the American College of Rheumatology（ACR） in 2014. The differences in the mRNA expression level of A20 and NLRP3 genes were compared between the newly diagnosed children and HCs. According to different treatment options，JIA patients were divided into IL-6 inhibitors group，TNF-α inhibitors group and non-biological agents group. The correlations between the expression of these two genes and the efficacy after six months of treatment were analyzed.Results The expression level of A20 in JIA group was significantly lower than that in HCs（P=0.039）. The expression level of A20 in systemic JIA（sJIA） group was lower than that in non-systemic JIA（non-sJIA） group（P=0.005）. There was no significant difference in the expression of NLRP3 gene between the two groups（P>0.05）. There was no significant correlation between the expression of A20 and NLRP3 gene with the therapeutic efficacy by the binary logistic regression analysis（P>0.05）. After six months’ treatment，NLRP3 expression in the CR group was lower than that of the clinical non-remission group（P<0.05），and there was no significant difference in A20 gene expression between CR group and non-remission group（P>0.05）.Conclusion The expression of A20 is significantly decreased in children with JIA. The expression of A20 in sJIA is lower than that in non-sJIA. Low expression of NLRP3 gene in children with JIA may have a higher treatment response rate and better prognosis. No correlation has been found between the expression of A20 and NLRP3 genes and the therapeutic efficacy of JIA yet.