慢性乙型肝炎病毒感染者T淋巴细胞和NK细胞T淋巴细胞免疫球蛋白黏蛋白分子3表达与肝脏炎症和纤维化相关性分析  

Correlation of Tim-3 expression on T lymphocytes and natural killer cells with hepatic inflammation and hepatic fibrosis in chronic hepatitis B patients

作　　者：李静[1] 顾玉荣[2] 毕燕华 黄月华[1,2] Li Jing;Gu Yurong;Bi Yanhua;Huang Yuehua(Guangdong Provincial Key Laboratory of Liver Diseases,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;Department of Infectious Diseases,the Third Affiliated Hospital of Sun Yat-sen,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院广东省肝脏病研究重点实验室,广州510630 [2]中山大学附属医第三院感染性疾病科,广州510630

出　　处：《中华临床感染病杂志》2021年第3期161-172,共12页Chinese Journal of Clinical Infectious Diseases

基　　金：国家自然科学基金(2014ZX10002002);广州市科技计划项目(202002030431)。

摘　　要：目的探究慢性乙型肝炎病毒(HBV)感染者T淋巴细胞及自然杀伤(NK)细胞T淋巴细胞免疫球蛋白黏蛋白分子3(Tim-3)表达及其在评估肝纤维化程度中的潜在价值。方法选取2016年6月1日至2018年6月1日于中山大学附属第三医院感染性疾病科门诊就诊的320例慢性HBV感染者,将其分成免疫耐受期组(31例),免疫活动期组(184例),非活动期组(48例)和灰色区组(57例);同时纳入17例健康志愿者作为健康对照组。分离每例研究对象外周血单个核细胞并采用流式细胞仪分别检测CD3+T淋巴细胞及其亚群(CD4+和CD8+T淋巴细胞)以及NK细胞及其亚群(NK-bright和NK-dim细胞)Tim-3表达频率和平均荧光强度(MFI)。收集患者临床资料并计算天冬氨酸转氨酶与血小板计数比值指数(APRI)。采用Kruskal-Wallis H检验进行多组间非正态分布计量资料比较,组间两两比较采用Mann-Whitney U检验。计数资料采用例(百分数)表示,采用卡方检验进行比较。相关性分析采用Spearman秩相关。采用受试者工作特征曲线(ROC)分析CD3+T淋巴细胞与NK细胞Tim-3表达比值在评估慢性乙型肝炎病毒(HBV)感染者肝纤维化进展中的预测价值。P<0.05为差异具有统计学意义。结果免疫耐受期、免疫活动期、非活动期、灰色区和健康对照组年龄、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、白蛋白(Alb)、总胆红素(TBil)和肝脏硬度差异均有统计学差异(H=12.40、169.70、210.70、25.17、24.21和86.50,P值均<0.05)。免疫耐受期、免疫活动期、非活动期和灰色区组APRI评分、乙型肝炎e抗原(HBeAg)阳性患者比例、乙型肝炎表面抗原(HBsAg)和HBV-DNA差异均有统计学差异(H=89.45、118.00和14.81,χ^(2)=148.20,P值均<0.05)。免疫耐受期、免疫活动期、非活动期、灰色区及健康对照组CD3+、CD4+和CD8+T淋巴细胞以及NK细胞、NK-bright和NK-dim细胞Tim-3表达频率及MFI差异均有统计学意义(H=13.57、51.55、8.58、4Objective To explore the correlation of the expression of lymphocyte immunoglobulin-mucin domain 3(Tim-3)on T lymphocytes and natural killer(NK)cells with hepatic inflammation and hepatic fibrosis in patients with chronic hepatitis B virus(HBV)infection.Methods A total of 320 patients of chronic HBV infection who visited the Infectious Diseases Department in the Third Affiliated Hospital of Sun Yat-sen University from June 2016 to June 2018 were enrolled.The patients were divided into four groups:immune tolerant group(IT,n=31),immune active group(IA,n=184),inactive carriers group(IC,n=48),and gray zone group(GZ,n=57).And 17 healthy controls(HC group)were included at the same time.Peripheral blood mononuclear cells were separated and the frequency and mean fluorescence intensity(MFI)of Tim-3 on T cells(CD3+,CD4+and CD8+T cells)and NK cells(NK,NK-bright and NK-dim cells)were detected by flow cytometry.The clinical data of patients were collected and aspartate aminotransferase-to-platelet ratio index(APRI)score was calculated.Kruskal-Wallis H test was used for comparing the data of non-normal distribution among groups,and Mann Whitney U test was used for the comparison between two groups.Enumeration data were expressed as cases(percentage)and compared by the Chi-square test.Spearman rank correlation was used for correlation analysis.Receiver operating characteristic curve(ROC)was used to analyze the predictive value of Tim-3 expression on T cells and NK cells in evaluating liver fibrosis in patients with chronic HBV infection.P<0.05 was considered statistically significant.Results Significant differences were found in the age,aspartate aminotransferase(AST),alanine aminotransferase(ALT),albumin(Alb),total bilirubin(TBil)and liver stiffness measurement(LSM)among IT,IA,IC,GZ and HC groups(H=12.40,169.70,210.70,25.17,24.21 and 86.5,all P<0.05).And the differences in APRI score,proportion of HBeAg-positive patients,HBsAg and HBV-DNA among the IT group,IA group,IC group,GZ group were also significant(H=89.45,118.00 and 1

关 键 词：T淋巴细胞 自然杀伤细胞 T淋巴细胞免疫球蛋白黏蛋白分子3 肝纤维化 肝炎 乙型 慢性 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]