川崎病患儿血清CaN、NFATc1水平与冠状动脉损伤及治疗效果的相关性分析

Correlation analysis of serum CaN and NFATc1 levels with coronary artery injury and treatment effect in children with Kawasaki disease

目的分析川崎病(KD)患儿血清钙调神经磷酸酶(CaN)、活化T细胞核因子c1(NFATc1)水平与冠状动脉损伤(CALs)及治疗效果的相关性。方法选择2018年6月—2021年6月昆明医科大学附属儿童医院/昆明市儿童医院感染科收治KD患儿106例(KD组),根据疗效分为无效亚组16例和有效亚组90例,另选择医院体检健康儿童38例为健康对照组。检测受试者血清CaN、NFATc1、白介素(IL)-6、肿瘤坏死因子-α(TNF-α)水平,外周血CD3^(+)、CD4^(+)、CD8^(+)T细胞占比及CD4^(+)/CD8^(+)比值,超声心动图测量左、右冠状动脉内径。分析血清CaN、NFATc1与IL-6、TNF-α、外周血CD3^(+)、CD4^(+)、CD8^(+)T细胞占比、CD4^(+)/CD8^(+)及左右冠状动脉内径、冠状动脉分级的相关性。绘制受试者工作特征曲线(ROC)分析血清CaN、NFATc1预测KD临床疗效的价值。结果KD组血清CaN、NFATc1、IL-6、TNF-α水平,CD8^(+)T细胞占比,左、右冠状动脉内径高于健康对照组(t/P=20.424/<0.001、8.080/<0.001、29.154/<0.001、15.762/<0.001、2.793/0.006、9.320/<0.001、10.885/<0.001),CD3^(+)、CD4^(+)T细胞占比、CD4^(+)/CD8^(+)低于健康对照组(t/P=6.872/<0.001、7.140/<0.001、12.758/<0.001)。无效亚组血清CaN、NFATc1水平高于有效亚组(t/P=8.368/<0.001、5.643/<0.001)。KD患儿血清CaN、NFATc1水平与IL-6、TNF-α水平,CD8^(+)T细胞占比、左冠状动脉内径、右冠状动脉内径、冠状动脉分级呈正相关(CaN:r/P=0.406/<0.001、0.321/<0.001、0.302/<0.001、0.419/<0.001、0.437/<0.001、0.502/<0.001;NFATc1:r/P=0.469/<0.001、0.353/<0.001、0.325/<0.001、0.386/<0.001、0.402/<0.001、0.528/<0.001),与CD3^(+)、CD4^(+)T细胞占比、CD4^(+)/CD8^(+)呈负相关(CaN:r/P=-0.396/<0.001、-0.285/0.009、-0.438/<0.001;NFATc1:r/P=-0.378/<0.001、-0.305/<0.001、-0.417/<0.001)。血清CaN、NFATc1及二者联合预测KD临床疗效的曲线下面积为0.709、0.688、0.852,二者联合高于单独检测(Z/P=3.417/0.001、2.588/0.010)。结论KD患儿血清CaN、NFATc1水平升高,且与细胞免疫功能紊乱、炎性反应、CALs及临床疗效有关。

Objective To analyze the correlation of serum calcineurin(CaN)and activated T cell nuclear factor c1(NFATc1)levels with coronary artery injury(CALs)and treatment effect in children with Kawasaki disease(KD).Methods From June 2018 to June 2021,106 children with KD(KD group)admitted to the Department of Infectious Diseases,Children’s Hospital Affiliated to Kunming Medical University/Kunming Children’s Hospital,were selected.In addition,38 healthy children who underwent physical examination in hospitals were selected as the healthy control group.The serum levels of CaN,NFATc1,interleukin(IL)6,tumor necrosis factorα(TNF-α),the proportion of CD3^(+),CD4^(+),CD8^(+)T cells in peripheral blood and the ratio of CD4^(+)/CD8^(+)were detected,and the left and right coronary arteries were measured by echocardiography.Arterial diameter.The correlation between serum CaN,NFATc1 and IL-6,TNF-α,peripheral blood CD3^(+),CD4^(+),CD8^(+)T cells,CD4^(+)/CD8^(+)ratio,left and right coronary artery diameter and coronary artery grade were analyzed.The receiver operating characteristic(ROC)curve was drawn to analyze the value of serum CaN and NFATc1 in predicting the clinical efficacy of KD.Results The serum levels of CaN,NFATc1,IL-6,TNF-α,the proportion of CD8^(+)T cells,and the inner diameter of the left and right coronary arteries in the KD group were higher than those in the healthy control group(t/P=20.424/<0.001,8.080/<0.001,29.154/<0.001,15.762/<0.001,2.793/0.006,9.320/<0.001,10.885/<0.001),the proportion of CD3^(+),CD4^(+)T cells,and the ratio of CD4^(+)/CD8^(+)were lower than those in the healthy control group(t/P=6.872/<0.001,7.140/<0.001,12.758/<0.001).Serum levels of CaN and NFATc1 in the ineffective subgroup were higher than those in the effective subgroup(t/P=8.368/<0.001,5.643/<0.001).Serum levels of CaN and NFATc1 in children with KD were positively correlated with levels of IL-6 and TNF-α,proportion of CD8^(+)T cells,left coronary artery diameter,right coronary artery diameter,and coronary artery grade(CaN:r/P=0.406/<0.001,0.321/<0.001,0.302/<0.001,0.419/<0.001,0.437/<0.001,0.502/<0.001;NFATc1:r/P=0.469/<0.001,0.353/<0.001,0.325/<0.001,0.386/<0.001,0.402/<0.001,0.528/<0.001),negatively correlated with the proportion of CD3^(+),CD4^(+)T cells,and the ratio of CD4^(+)/CD8^(+)(CaN:r/P=-0.396/<0.001,-0.285/0.009,-0.438/<0.001;NFATc1:r/P=-0.378/<0.001,-0.305/<0.001,-0.417/<0.001).The areas under the curve of serum CaN,NFATc1 and their combination to predict the clinical efficacy of KD were 0.709,0.688,and 0.852,and the combination of the two was higher than the single detection(Z/P=3.417/0.001,2.588/0.010).Conclusion Serum levels of CaN and NFATc1 in children with KD increased,and were related to cellular immune dysfunction,inflammatory response,CALs and clinical efficacy.