循环滤泡型辅助性T淋巴细胞及IL-21在自身免疫性肝炎中的初步研究

Preliminary study of the T follicular helper cells and interleukin-21 in patients with autoimmune hepatitis

目的检测外周血滤泡型辅助性T淋巴细胞百分率(Tfh)及细胞上CCR7、PD-1、IL-21R等分子的表达水平,血清IL-21的表达水平,为进一步研究Tfh细胞及其相关分子在自身免疫性肝炎发病机制中的作用提供实验依据。方法收集20例自身免疫性肝炎患者与20例健康志愿者外周抗凝血,流式细胞仪检测循环Tfh细胞百分率与细胞膜上CCR7,PD-1,IL-21R等分子的表达水平,并进一步分析CCR7+Tfh亚型细胞上PD-1、IL-21R等分子的表达水平,同时ELISA检测外周血血清IL-21的水平;统计分析健康对照与自身免疫性肝炎患者的外周血Tfh细胞百分率、细胞膜上PD-1与IL-21R分子表达水平,血清IL-21表达水平的差异。结果 1)循环Tfh细胞百分率在健康对照(4.793%±1.5609%)与自免肝患者(8.915%±3.235%)具有显著性差别;循环Tfh细胞表达的PD-1分子(健康对照:91.173%±5.032%,自免肝患者:5.177%±3.267%)与IL-21R(健康对照97.625%±1.137%,自免肝患者27.800%±7.918%)具有显著性差别;2)外周血血清IL-21水平[健康对照(:444.75±75.05)pg/ml,自免肝患者(:862.80±109.83)pg/ml]也具有显著性差别;3)自身免疫性肝炎患者循环Tfh细胞百分率与血清GGT、ALP呈正相关与细胞上的PD-1表达水平呈负相关,后者与血清TB呈正相关。结论 Tfh细胞及其表达的相关分子(PD-1,IL-21R)在健康人与自免肝患者的表达水平是不同的,可能参与介导了自身免疫性肝炎的发生与发展。

In this study,we aimed to characterize peripheral Tfh cells and serum IL-21,and evaluate their association with liver function in autoimmune hepatitis（AIH）.Total of 20 AIH patients and 20 healthy volunteers were recruited in this study.A fluorescence-activated cell sorter（FACS） was used to detect the percentage of Tfh cells and the levels of the PD-1,IL-21R,and CCR7 expressed on the cells;ELISA was used to detect the levels of serum IL-21.We found that the percentage of Tfh cells and the level of serum IL-21 increased but both the expressions of PD-1 and IL-21R on Tfh cells decreased in AIH patients,as compared with health volunteers;the percentage of circular Tfh cells is positively related with serum alkaline phosphatase（ALP） and gama-glutamyltransferase（GGT） in AIH patients,but negatively related with PD-1 expressed on Tfh cells,The level of PD-1 expressed on Tfh cells was positively correlated with serum TB.All results indicate that T follicular helper cells,the PD-1,IL-21R,and the serum IL-21 may participates in the development of autoimmune hepatitis.