HBV相关慢加急性肝衰竭患者外周血CD3^+CD56^+自然杀伤T淋巴细胞中TIM-3的表达及意义  

Expression and significance of T-cell immunoglobulin and mucin domain-containing molecule 3 in peripheral blood CD3^+CD56^+ natural killer T cells in patients with hepatitis B virus-related acute-on-chronic liver failure

作　　者：高梦丹 覃岭[1] 孙坚萍[1] 李康[1] 李昂[1] 娄金丽[1] 张永宏[1] 赵艳[1] GAO Mengdan;QIN Ling;SUN Jianping(Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China)

机构地区：[1]首都医科大学附属北京佑安医院临床检验中心

出　　处：《临床肝胆病杂志》2019年第9期2006-2010,共5页Journal of Clinical Hepatology

基　　金：北京市医管局“扬帆计划”重点专业(ZYLX201711);十三五国家传染病重大专项(2017ZX10202102-003-003);北京市医院管理局“登峰”计划专项经费资助(DFL20181701);十二五(旷博)基于传染病发生、发展临床分期的血清microRNA表达谱系列诊断试剂盒研发(2015ZX10004801-001)

摘　　要：目的探讨HBV相关慢加急性肝衰竭(HBV-ACLF)患者外周血自然杀伤T淋巴细胞(NKT细胞)数量及T淋巴细胞免疫球蛋白和黏蛋白结构域3(TIM-3)表达水平与患者肝损伤及预后的相关性。方法收集2016年9月-2018年6月在首都医科大学附属北京佑安医院接受治疗的43例HBV-ACLF患者和28例慢性乙型肝炎(CHB)患者的外周血单个核细胞,采用流式细胞技术检测患者外周血CD3^+CD56^+NKT细胞数量及其TIM-3表达水平。呈正态分布的计量资料2组间比较采用t检验;非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ^2检验,相关性分析采用Pearson相关系数。结果 HBV-ACLF组ALT、AST、TBil、Cr、INR、HBV DNA、TBil/ALT比值及MELD评分等指标明显高于CHB组,Alb、PTA指标明显低于CHB组(P值均<0.05)。HBV-ACLF患者外周血CD3^+CD56^+NKT细胞数量为明显低于CHB组[(19.13±13.82)%vs (26.75±11.84)%,t=2.401,P=0.019],HBV-ACLF组CD3^+CD56^+NKT细胞TIM-3表达水平明显高于CHB组[5.53%(2.95%~10.20%) vs 1.59%(0.91%~2.70%),Z=-5.260,P<0.001]。CD3^+CD56^+NKT细胞TIM-3表达水平与ALT、AST、MELD评分、INR呈正相关(r值分别为0.637、0.414、0.355、0.335,P值分别为<0.000 1、0.006、0.021、0.031),与PTA%呈负相关(r=-0.313,P=0.043)。43例HBV-ACLF患者中,早期患者为12例、中期患者为21例、晚期患者为10例,3组间CD3^+CD56^+NKT细胞数量比较差异均无统计学意义(P值均> 0.05),但呈增高趋势。中、晚期HBV-ACLF患者CD3^+CD56^+NKT细胞TIM-3表达水平分别为6.50%(3.16%~11.45%)、8.56%(4.00%~10.93%),均明显高于早期2.58%(1.92%~6.02%)(Z值分别为-2.284、-2.641,P值均<0.05)。43例患者28 d存活组CD3^+CD56^+NKT细胞TIM-3表达水平明显低于28 d肝移植/死亡组[2.98%(1.94%~6.88%) vs 8.56%(4.27%~11.43%),Z=-2.831,P=0.005]。结论 HBV-ACLF患者外周血CD3^+CD56^+NKT细胞TIM-3表达水平增高,与患者肝损伤程度及预后相关。Objective To investigate the expression of T-cell immunoglobulin and mucin domain-containing molecule 3( TIM-3) in natural killer T( NKT) cells and its association with liver injury and prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure( HBV-ACLF).Methods Peripheral blood mononuclear cells were isolated from 43 patients with HBV-ACLF and 28 patients with chronic hepatitis B( CHB) who were treated in Beijing YouAn Hospital,Capital Medical University,from September 2016 to June 2018,and flow cytometry was used to measure the number of peripheral blood CD3^+CD56^+NKT cells and the expression of TIM-3.The t-test was used for comparison of normally distributed continuous data between two groups.The Kruskal-Wallis H test was used for comparision of non-normally distributed continuous data between multiple groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between groups,and the Pearson correlation coefficient was used to investigate correlation.Results Compared with the CHB group,the HBV-ACLF group had significantly higher alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBil),creatinine,international normalized ratio( INR),HBV DNA,TBil/ALT ratio,and Model for End-Stage Liver Disease( MELD) score,as well as significantly lower albumin and prothrombin time activity( PTA)( all P<0.05).Compared with the CHB group,the HBV-ACLF grouphad a significantly higher number of CD3^+CD56^+NKT cells( 19.13%± 13.82% vs 26.75%± 11.84%,t = 2.401,P = 0.019) and significantly higher expression of TIM-3 in CD3^+CD56^+NKT cells [5.53%( 2.95%-10.2%) vs 1.59%( 0.91%-2.7%),Z =-5.260,P<0.001].The expression of TIM-3 in CD3^+CD56^+NKT cells was positively correlated with ALT( r = 0.637,P<0.000 1),AST( r = 0.414,P = 0.006),INR( r = 0.335,P = 0.031),and MELD score( r = 0.355,P = 0.021) and was negatively correlated with PTA%( r =-0.313,P = 0.043).Am

关 键 词：乙型肝炎 慢加急性肝功能衰竭 杀伤细胞 天然 预后 

分 类 号：R512.62[医药卫生—内科学] R575.3[医药卫生—临床医学]