HBV相关慢加急性肝衰竭患者Treg细胞、Th17细胞表达特点及其与HBV前C区/BCP区变异的相关性

肝脏 ›› 2018, Vol. 23 ›› Issue (1): 18-21.

HBV相关慢加急性肝衰竭患者Treg细胞、Th17细胞表达特点及其与HBV前C区/BCP区变异的相关性

高海兵, 王香梅, 刘宝荣, 潘晨, 方建凯, 林升龙, 马华皙, 陈秀敏, 林明华, 郑瑞丹

350025 福州福建医科大学孟超肝胆医院,福州市传染病医院,福建医科大学附属传染病医院肝内科,福州市感染病学临床重点专科(高海兵,王香梅,刘宝荣,潘晨,方建凯,林升龙,马华皙,陈秀敏,林明华);漳州正兴医院肝病内科(郑瑞丹)

收稿日期:2017-09-14 发布日期:2020-04-30
通讯作者: 林明华,Email:lmh543@163.com;郑瑞丹,Email:zhengruidan@tom.com
基金资助:
福建省医学创新课题(2015-CXB-29),福建医科大学非直属附属医院科研发展专项基金资助(FZS13002Y), 福建省卫生计生中青年骨干人才培养项目(2016-ZQN-77),福州市临床重点专科建设项目经费资助(201510301),福州市卫生系统科技计划项目(2014-S-w26)

Expression of Treg and Th17 in HBV-related acute-on-chronic liver failure patients and their correlations with the mutations in HBV pre-C/BCP region

GAO Hai-bing, WANG Xiang-mei, LIU Bao-rong, PAN Chen, FANG Jian-kai, LIN Sheng-long, MA Hua-xi, CHEN Xiu-min, LIN Ming-hua, ZHENG Rui-dan

Department of Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou Municipal Infectious Disease Hospital, the Affiliated Infectious Diseases Hospital of Fujian Medical University, Fuzhou 350025,China(Gao HB,Wang XM,Liu BR,Pan C,Fang JK,Lin SL,Ma HX,Chen XM,Lin MH);Department of Hepatology,Zhangzhou Zhengxing Hospital,Zhangzhou 363000,China(Zheng RD)

Received:2017-09-14 Published:2020-04-30
Contact: Lin Minghua, Email:lmh543@163.com; Zheng Ruidan, Email: zhengruidan@tom.com

摘要/Abstract

摘要： 目的探讨HBV相关慢加急性肝衰竭患者外周血调节性T淋巴细胞(Treg)、辅助性T淋巴细胞(Th)17细胞表达特点及其与HBV前C区/BCP区变异的相关性。方法选择HBV相关慢加急性肝衰竭和肝衰竭前期患者各41例,采用ELISA 检测外周血IL-17、TGF-β1、IFN-γ、IL-1β及IL-21水平,流式细胞术检测Treg和Th17表达水平,直接测序法检测HBV前 C 区及BCP区基因,统计学处理用t检验。结果肝衰竭患者Treg、Th17、IL-17、TGF-β1、IFN-γ、IL-1β水平、HBV变异位点中A1762T/G1764A双突变、G1896A突变比例分别为(9.28±1.12)%、(0.23±0.05)%、(151.83±35.22) pg/mL、(153.24±34.15) pg/mL、(177.61±29.25) pg/mL、(77.46±13.15) pg/mL、22/19、23/18,均高于肝衰竭前期患者的(7.47±0.74)%、(0.19±0.03)%、(134.02±34.39) pg/mL、(130.76±35.13) pg/mL、(130.68±22.87) pg/mL、(60.12±15.67) pg/mL、13/28、12/29,差异均有统计学意义(t’值分别为8.594、4.609、2.316、2.939、8.094、5.429,χ²值分别为4.038、6.032,均P<0.05);而Treg/Th17比值、IL-21水平在两组中差异无统计学意义(t=0.902,P=0.370;t=0.294,P=0.769)。HBV BCP区A1762T/G1764A双突变和G1896A突变的患者Treg、Th17水平均高于野生型,差异有统计学意义(t=2.932,P=0.004;t=2.339,P=0.022;t=3.232,P=0.002;t’=2.990,P=0.004),而Treg/Th17比值在突变型和野生型中差异均无统计学意义(t=0.030,P=0.976;t’=0.272,P=0.787)。结论 Treg细胞及Th17细胞变化,HBV BCP区A1762T/G1764A双突变、G1896A突变可能与HBV相关慢加急性肝衰竭相关。

关键词: 乙型肝炎病毒, 肝功能衰竭, T淋巴细胞,调节性, 辅助性T淋巴细胞17, 突变

Abstract: Objective To investigate the expression characteristics of peripheral T regulatory cell (Treg) and T help cell 17 (Th17) in patients with hepatitis B related acute-on-chronic liver failure (HBV-ACLF), and their correlation with HBV pre-C/BCP mutations.Methods Forty-one HBV-ACLF patients and 41 early ACLF patients were enrolled. Levels of serum interleukin (IL)-17, transforming growth factor (TGF)-β1, interferon (IFN)-γ, IL-1β and IL-21 were determined using enzyme-linked immuno sorbent assay (ELISA). Expression of Treg and Th17 were determined using flow cytometry. Sequencing for mutations of HBV pre-C/BCP region was performed. Results Levels of Treg, Th17, IL-17, TGF-β1, IFN-γ and IL-1β, A1762T/G1764A double mutations and G1896A mutation were significantly higher in HBV-ACLF patients than those in early HBV-ACLF patients (t' = 8.594, P<0.001; t = 4.609, P<0.001; t=2.316, P=0.023; t=2.939, P=0.004; t=8.094, P<0.001; t=5.429,P<0.001; χ²=4.038, P=0.044; χ²=6.032, P=0.01), respectively. There were no significant difference in the ratio of Treg/Th17 and IL-21 level between HBV-ACLF and early HBV-ACLF group (t=0.902, P=0.370; t=0.294, P=0.769). Treg and Th17 levels in patients with A1762T/G1764A double mutations or G1896A mutation were both significantly higher than those with no mutations (t=2.932, P=0.004; t=2.339, P=0.022; t=3.232, P=0.002; t'=2.990, P=0.004). There were no significant difference in the ratio of Treg/Th17 between mutation and non-mutation groups (t=0.030, P=0.976; t'=0.272, P=0.787). Conclusion Changes of Treg and Th17, A1762T/G1764A double mutations in HBV BCP region and G1896A mutation in pre-C region might play roles in pathogenesis of HBV-ACLF.

Key words: Hepatitis B virus, Liver failure, T regulatory cell, T helper cells 17, Mutation

高海兵, 王香梅, 刘宝荣, 潘晨, 方建凯, 林升龙, 马华皙, 陈秀敏, 林明华, 郑瑞丹. HBV相关慢加急性肝衰竭患者Treg细胞、Th17细胞表达特点及其与HBV前C区/BCP区变异的相关性[J]. 肝脏, 2018, 23(1): 18-21.

GAO Hai-bing, WANG Xiang-mei, LIU Bao-rong, PAN Chen, FANG Jian-kai, LIN Sheng-long, MA Hua-xi, CHEN Xiu-min, LIN Ming-hua, ZHENG Rui-dan. Expression of Treg and Th17 in HBV-related acute-on-chronic liver failure patients and their correlations with the mutations in HBV pre-C/BCP region[J]. Chinese Hepatolgy, 2018, 23(1): 18-21.

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