A20及NLRP3基因在幼年特发性关节炎中的表达及临床意义探讨

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

摘要:

目的 比较A20及NLRP3基因在幼年特发性关节炎（juvenile idiopathic arthritis，JIA）患儿及健康儿童中的表达差异，探讨其在预测JIA患儿生物制剂疗效中的作用。方法 依据2001年国际风湿病学联盟诊断标准，收集68例初诊JIA患儿及同期33例健康儿童外周血提取单个核细胞，采用实时荧光定量PCR（quantitative real-time PCR，qRT-PCR）检测A20及NLRP3基因mRNA表达水平。依据美国风湿病学会2014年提出的JIA疾病活动度评分，将疾病无活动状态视为临床缓解。比较初诊时JIA患儿及健康儿童A20及NLRP3基因mRNA表达水平差异。根据不同治疗选择分为白细胞介素-6受体拮抗剂组、肿瘤坏死因子-α抑制剂组及非生物制剂组，随访两基因表达与治疗6个月后疗效之间的相关性。结果 初诊时，相比于健康对照组，JIA组A20基因表达水平明显降低（P=0.039），全身型JIA（systemic JIA，sJIA）组A20基因表达水平低于非全身型JIA（non-systemic JIA，non-sJIA）组（P=0.005）；2组NLRP3基因表达未见统计学差异（P>0.05）；采用二分类logistic回归分析未发现初诊JIA组A20及NLRP3基因表达水平与JIA治疗疗效具有相关性（组间比较P>0.05）；随访6个月后临床缓解组初诊NLRP3基因表达水平低于临床未缓解组（P<0.05），初诊A20基因表达在临床缓解组与未缓解组中未见统计学差异（P>0.05）。结论 A20基因在初诊JIA患儿中表达降低，sJIA组A20基因表达水平低于non-sJIA组，NLRP3基因低表达JIA患儿治疗缓解率更高，预后可能更好。暂未发现A20及NLRP3基因水平与JIA治疗效果的相关性。

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.