CD4+NKG2D+ T细胞在幼年特发性关节炎疾病活动中的作用

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis

摘要:

目的 分析幼年特发性关节炎（juvenile idiopathic arthritis，JIA）活动期及稳定期CD4⁺NKG2D⁺ T细胞及NKG2D可溶性配体，即可溶性MHC-Ⅰ类链相关分子A和B（soluble MHC class I chain-related molecules A/B，sMICA/sMICB）表达水平，探讨其在JIA疾病活动中的作用。方法 前瞻性纳入2019年11月—2021年12月重庆医科大学附属儿童医院确诊的全身型JIA 19例和关节型JIA 20例，6例健康儿童为对照组。收集外周血标本，采用酶联免疫吸附法测定sMICA和sMICB水平，采用流式细胞术检测CD4⁺NKG2D⁺ T细胞比例，采用全身型幼年关节炎疾病活动评分-27（systemic Juvenile Arthritis Disease Activity Score，sJADAS-27）/幼年关节炎疾病活动评分-27（Juvenile Arthritis Disease Activity Score-27，JADAS-27）评估JIA患儿的疾病活动性。采用Pearson相关分析法、受试者工作特征曲线分析CD4⁺NKG2D⁺ T细胞及sMICA、sMICB在JIA疾病活动中的作用。结果 全身型JIA活动期组及关节型JIA活动期组CD4⁺NKG2D⁺ T细胞比例较对照组及各自稳定期组升高（P<0.05）。JIA各组sMICA和sMICB水平均高于对照组（P<0.05）。关节型JIA活动期组sMICB水平高于关节型JIA稳定期组（P<0.05）。JIA患儿CD4⁺NKG2D⁺ T细胞比例及sMICA、sMICB水平与sJADAS-27/JADAS-27评分呈正相关（P<0.05）。sMICB对JIA疾病活动性评估的曲线下面积为0.755，特异度为0.90，灵敏度为0.64。结论 JIA患儿CD4⁺NKG2D⁺ T细胞比例及sMICA、sMICB水平较健康儿童升高，且与疾病活动性呈正相关，提示CD4⁺NKG2D⁺ T细胞及NKG2D配体可作为JIA疾病活动性评估的新指标。

Abstract:

Objective To study the expression levels of CD4⁺NKG2D⁺ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA.Methods Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4⁺NKG2D⁺ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4⁺NKG2D⁺ T cells, sMICA and sMICB in the disease activity of JIA.Results The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4⁺NKG2D⁺ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4⁺NKG2D⁺ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64.Conclusions The percentage of CD4⁺NKG2D⁺ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4⁺NKG2D⁺ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.