细胞因子失衡在全身型幼年特发性关节炎合并巨噬细胞活化综合征中的意义

Significance of cytokine imbalance in systemic onset juvenile idiopathic arthritis combined with macrophage activation syndrome

目的分析全身型幼年特发性关节炎(SOJIA)合并巨噬细胞活化综合征(MAS)患儿细胞因子谱,探讨其在早期诊断MAS中的临床意义。方法回顾性分析浙江省台州医院2013年1月至2018年3月157例SOJIA患儿的临床资料,其中合并MAS 15例(SOJIA合并MAS组),未合并MAS 142例(单纯SOJIA组)。采用流式细胞微球芯片技术检测患儿外周血白细胞介素(IL)-2、IL-4、IL-6、肿瘤坏死因子(TNF)-α和干扰素(IFN)-γ。分析MAS患儿细胞因子谱的特点。结果SOJIA合并MAS组IL-10和IFN-γ明显高于单纯SOJIA组[40.5(7.9,236.9)ng/L比4.1(2.0,98.7)ng/L和55.8(18.5,500.0)ng/L比4.4(1.4,30.1)ng/L],差异有统计学意义(P<0.01);两组IL-2、IL-4、IL-6和TNF-α比较差异无统计学意义(P>0.05)。Pearson相关性分析结果显示,SOJIA合并MAS患儿IL-10与IFN-γ呈正相关(r=0.638,P=0.011)。受试者工作特征曲线分析结果显示,IFN-γ预测MAS的曲线下面积(AUC)为0.991,95%CI 0.974~1.000,最佳临界值18.45 ng/L,灵敏度为92.5%,特异度为95.1%;IL-10预测MAS的AUC为0.944,95%CI 0.893~0.996,最佳临界值7.75 ng/L,灵敏度为91.7%,特异度为81.7%。结论SOJIA患儿IL-10和IFN-γ明显升高有助于MAS的早期诊断。

Objective To analyze cytokine pattern of systemic onset juvenile idiopathic arthritis(SOJIA)combined with macrophage activation syndrome(MAS)in children,and study the early diagnostic value in MAS.Methods The clinical data of 157 children with SOJIA from January 2013 to March 2018 in Taizhou Hospital of Zhejiang Province were retrospectively analyzed.Among them,SOJIA combined with MAS was in 15 cases(SOJIA combined with MAS group),and simple SOJIA was in 142 cases(simple SOJIA group).The peripheral blood levels of interleukin(IL)-2,IL-4,IL-6,tumor necrosis factor(TNF)-αand interferon(IFN)-γwere measured by flow cytometry cytometric beads array.The characteristics of cytokine pattern was analyzed.Results The IL-10 and IFN-γin SOJIA combined with MAS group were significantly higher than those in simple SOJIA group:40.5(7.9,236.9)ng/L vs.4.1(2.0,98.7)ng/L and 55.8(18.5,500.0)ng/L vs.4.4(1.4,30.1)ng/L,and there were statistical differences(P<0.01);there were no statistical difference in IL-2,IL-4,IL-6 and TNF-αbetween 2 groups(P>0.05).Pearson correlation analysis result showed that IL-10 was positive correlated with IFN-γin SOJIA children with MAS(r=0.638,P=0.011).Receiver operating characteristic curve analysis result showed that the area under the curve(AUC)of IFN-γin predicting MAS was 0.991,95%CI 0.974 to 1.000,the optimal critical value was 18.45 ng/L,the sensitivity was 92.5%,and the specificity was 95.1%;the AUC of IL-10 in predicting MAS was 0.944(95%CI 0.893 to 0.996),the optimal critical value was 7.75 ng/L,the sensitivity was 91.7%,and the specificity was 81.7%.Conclusions The significant increased IL-10 and IFN-γis helpful for the early diagnosis MAS in children with SOJIA.