原发性胆汁性胆管炎患者外周血Treg/Th17细胞相关细胞因子水平变化

Diagnostic performance of peripheral blood Treg/Th17 cells and their related cytokines in predicting significant liver fibrosis in patients with primary biliary cholangitis

目的探讨外周血调节性T淋巴细胞(Treg)/辅助性T淋巴细胞17(Th17)相关细胞因子评估原发性胆汁性胆管炎(PBC)显著性肝纤维化的价值。方法2019年1月~2021年12月我院收治的PBC患者59例和同期健康体检者59例,PBC患者均接受肝穿刺活检,使用流式细胞仪检测外周血Treg/Th17细胞百分比,采用ELISA法检测血清白细胞介素(IL)-10、IL-6和IL-17水平,应用SPSS 20.0软件绘制受试者工作特征曲线(ROC),以曲线下面积(AUC)评估各指标诊断PBC患者显著性肝纤维化的效能。结果PBC患者外周血Treg细胞比率、Th17细胞比率和Th17/Treg细胞比值分别为(3.1±0.5)%、(5.9±0.9)%和(1.9±0.3),均显著高于健康人【分别为(1.6±0.3)%、(2.3±0.5)%和(1.4±0.1),P<0.05】;PBC患者血清IL-10、IL-6和IL-17水平分别为(19.5±3.4)ng/L、(10.3±2.2)ng/L和(21.2±3.1)ng/L,均显著高于健康人【分别为(13.9±2.7)ng/L、(6.4±1.5)ng/L和(5.1±0.9)ng/L,P<0.05】;肝组织病理学检查显示,本组PBC患者存在非显著性肝纤维化20例,显著性肝纤维化组39例;显著性肝纤维化患者外周血Treg细胞比率、Th17细胞比率和Th17/Treg细胞比值均显著高于非显著性肝纤维化患者(P<0.05);显著性肝纤维化患者血清IL-10、IL-6和IL-17水平均显著高于非显著性肝纤维化患者(P<0.05);经ROC曲线分析结果显示,联合外周血Treg细胞比率、Th17细胞比率、Treg/Th17比值、血清IL-10、IL-6和IL-17水平等6项指标诊断PBC患者显著性肝纤维化的AUC为0.956,显著高于六项指标的单独评估(分别为0.760、0.746、0.776、0.747、0.736和0.769,P<0.05)。结论PBC患者外周血Treg和Th17细胞及其细胞因子水平发生了显著的变化,而这种变化高度提示肝纤维化的存在,其诊断肝纤维化的应用值得进一步研究。

Objective The aim of this study was to explore the diagnostic efficacy of peripheral blood regulatory T cells(Treg)/helper T cells 17(Th17)and theirrelated cytokines in predicting significant liver fibrosis in patients with primary biliary cholangitis(PBC).Methods 59 patients with PBC and 59 healthy persons were encountered in our hospital between January 2019 and December 2021.All PBC patients underwent routine liver biopsy.The percentages of peripheral blood Treg/Th17 cells were detected by flow cytometry.Serum IL-10,IL-6 and IL-17 levels were detected by ELISA.The receiver operating characteristic(ROC)curves were drawn by SPSS 20.0 software,and the diagnostic performance of peripheral blood Treg/Th17 cell’s parameters in predicting significant liver fibrosis was evaluated by area under the curve(AUC).Results The percentages of peripheral blood Treg and Th17 cells,and Th17/Treg cell ratio in patients with PBC were(3.1±0.5)%,(5.9±0.9)%and(1.9±0.3),all significantly higher than[(1.6±0.3)%,(2.3±0.5)%and(1.4±0.1),respectively,P<0.05]in healthy persons;serum IL-10,IL-6 and IL-17 levels in patients with PBC were(19.5±3.4)ng/L,(10.3±2.2)ng/L and(21.2±3.1)ng/L,all significantly higher than[(13.9±2.7)ng/L,(6.4±1.5)ng/L and(5.1±0.9)ng/L,respectively,P<0.05]in healthy persons;the liver histopathological examination showed non-significant liver fibrosis in 20 cases,and significant liver fibrosis in 39 cases in our series;the percentages of cells and their related serum cytokine levels in patients with significant liver fibrosis were much higher than in those with non-significant liver fibrosis(P<0.05);the ROC analysis demonstrated that the AUC was 0.956 when all the six parameter combination in predicting significant liver fibrosis in patients with PBC,much higher than 0.760,0.746,0.776,0.747,0.736 and 0.769(P<0.05)by any one of them.Conclusion The percentages of peripheral blood Treg and Th17 cells,and their related serum cytokine levels increase in patients with PBC,which might be related to liver fibrosis,and needs further investigation.