慢性乙型肝炎患者肝内TCR文库在核苷(酸)类似物治疗前后的变化及意义

肝脏 ›› 2021, Vol. 26 ›› Issue (7): 742-746.

慢性乙型肝炎患者肝内TCR文库在核苷(酸)类似物治疗前后的变化及意义

吴宏楷, 邓浩辉, 龚明星, 高洪波, 王战会, 于乐成

510120 广东广州医科大学,广州医科大学附属第一医院,呼吸疾病国家重点实验室(吴宏楷);广州市第八人民医院(邓浩辉,高洪波);南方医科大学南方医院感染内科(龚明星,王战会);东部战区总医院感染病科/肝病治疗中心(于乐成)

收稿日期:2021-06-05 出版日期:2021-07-31 发布日期:2021-09-02
通讯作者: 王战会,Email: wangzhh@smu.edu.cn;于乐成,Email: gslsycy@163.com
基金资助:
广州市科技计划项目(201803010041)

Dynamic changes of intrahepatic T cell receptor repertoires before and after nucleos(t)ide analogues treatment in patients with chronic hepatitis B

WU Hong-kai, DENG Hao-hui, GONG Ming-xing, GAO Hong-bo, WANG Zhan-hui, YU Le-cheng

State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangdong 510120, China

Received:2021-06-05 Online:2021-07-31 Published:2021-09-02
Contact: WANG Zhan-hui, Email: wangzhh@smu.edu.cn

摘要/Abstract

摘要： 目的研究慢性乙型肝炎(CHB)患者经核苷(酸)类似物(NUCs)治疗前后肝内T细胞受体(TCR)文库变化特征。方法选取10例接受替比夫定(LdT)治疗的CHB患者,根据治疗104周后是否发生HBeAg血清学转换分为两组。通过高通量测序分析LdT治疗前后肝穿刺组织中TCRβ CDR3区,并分析TCR文库特征及其与血清学参数相关性。结果经过104周NUCs治疗,发生HBeAg血清学转换的CHB患者肝内TCR文库不重复VJ组合(151.0比71.0,P=0.043)、CDR3克隆型(223.0比109.0,P=0.043),以及标准化香农熵(0.58比0.17,P=0.043)均表现为文库多样性显著下降,同时这些患者治疗前后HBsAg的变化程度与消失克隆型变化呈正相关(r=0.9,P=0.037)。结论 CHB患者口服NUCs治疗可引起肝内TCR文库发生有利于特定T细胞克隆增生的变化,这对于促进HBeAg血清学转换有重要意义,提示在NUCs抗病毒治疗的基础上联合免疫治疗可能会更有助于HBV的控制。

关键词: 慢性乙型肝炎, T细胞受体β, 高通量测序

Abstract: Objective To investigate the dynamic changes of intrahepatic T cell receptor (TCR) repertoires before and after nucleos(t)ide analogues (NUCs) antiviral therapy in chronic hepatitis B (CHB) patients. Methods A total of ten CHB patients with tebivudine (LDT) based therapy were subdivided to two groups on HBeAg status after 104 treatment. The TCRβ complementarity determining region 3 (CDR3) of liver biopsies before and after 2-year NUCs treatment was analyzed by high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed. Results After LDT-based treatment for 104 weeks, the diversity of intrahepatic TCR repertoires in patients with HBeAg seroconversion decreased significantly on the number of unique VJ combinations (151.0 比 71.0, P=0.043), CDR3 clonotypes (223.0 比 109.0, P=0.043), and the values of normalized Shannon diversity entropy (0.58 比 0.17, P=0.045). The decline of HBsAg levels in these patients was positively correlated with the elevation of ablated clonetype frequency (r=0.9, P=0.037). Conclusion NUCs antiviral therapy may induce changes of intrahepatic TCR repertoires. T cell clone expansion plays an important role in HBeAg seroconversion, suggesting that oral antiviral therapy combined with immunotherapy may be more conducive to the control of HBV.

Key words: Chronic hepatitis B, T cell receptor β, High throughput sequencing

吴宏楷, 邓浩辉, 龚明星, 高洪波, 王战会, 于乐成. 慢性乙型肝炎患者肝内TCR文库在核苷(酸)类似物治疗前后的变化及意义[J]. 肝脏, 2021, 26(7): 742-746.

WU Hong-kai, DENG Hao-hui, GONG Ming-xing, GAO Hong-bo, WANG Zhan-hui, YU Le-cheng. Dynamic changes of intrahepatic T cell receptor repertoires before and after nucleos(t)ide analogues treatment in patients with chronic hepatitis B[J]. Chinese Hepatolgy, 2021, 26(7): 742-746.

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