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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
文章发布日期:2019年08月19日  来源:  作者:高梦丹,覃岭,孙坚萍,等  点击次数:93次  下载次数:11次

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【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χ2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。
【Abstract】:ObjectiveTo investigate the expression of T-cell immunoglobulin- and mucin domain-3-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). MethodsPeripheral 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. ResultsCompared 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 group had 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<0.0001), 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). Among the 43 patients with HBV-ACLF, 12 had early-stage HBV-ACLF, 21 had middle-stage HBV-ACLF, and 10 had advanced HBV-ACLF, and there was no significant difference in the number of CD3+CD56+ NKT cells between the three groups (all P>0.05), but with a tendency of increase; the patients with middle-stage or advanced HBV-ACLF had significantly higher expression of TIM-3 in CD3+CD56+ NKT cells than those with early-stage HBV-ACLF [6.5% (3.16%-1145%)/8.56% (4%-10.93%) vs 2.58% (1.92%-6.02%), Z=-2.284,-2.641, all P<005]. Among the 43 patients with HBV-ACLF, the 28-day survival group had significantly lower expression of TIM-3 in CD3+CD56+ NKT cells than the 28-day liver transplantation/death group [2.98% (1.94%-6.88%) vs 8.56% (4.27%-11.43%), Z=-2.831, P=0.005]. ConclusionThere is an increase in the expression of TIM-3 in peripheral blood CD3+CD56+ NKT cells in patients with HBV-ACLF, which is associated with the degree of liver injury and prognosis.
【关键字】:乙型肝炎; 慢加急性肝功能衰竭; 杀伤细胞, 天然; 预后
【Key words】:hepatitis B; acute-on-chronic liver failure; killer cells, natural; prognosis
【引证本文】:GAO MD, QIN L, SUN JP, et al. 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[J]. J Clin Hepatol, 2019, 35(9): 2006-2010. (in Chinese)
高梦丹, 覃岭, 孙坚萍, 等. 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[J]. 临床肝胆病杂志, 2019, 35(9): 2006-2010.

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