恩替卡韦治疗期间与乙型肝炎E抗原血清转化有关的不同T细胞

StephenW

Distinct T-Cell Receptor Profiles Associated With Hepatitis B E Antigen Seroconversion During Entecavir Treatment
Yi-Fan Lian  1 , Ying Xu  2 , Yu-Rong Gu  3 , Bi Yan-Hua  1 , Liao Chun-Hong  1 , Zhao Miao-Xian  2 , Xia-Lin Liao  1 , Zhan-Hui Wang  2 , Wu Hong-Kai  4 , Yue-Hua Huang  1   3
Affiliations
Affiliations

    1
    Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
    2
    State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    3
    Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
    4
    State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.

    PMID: 32564486 DOI: 10.1111/liv.14566

Abstract

Background & aims: T-cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during anti-virus therapy. We tried to assess TCR repertoire dynamics and its clinical significance upon HBeAg seroconversion in CHB patients.

Methods: Twenty CHB patients undergoing 1-year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non-complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRβ complementarity-determining region 3 (CDR3) of peripheral CD4+ and CD8+ T cells at weeks 0, 12 and 48 was analyzed by unbiased high-throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed.

Results: The diversity of TCRβ repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4+ subset but later at week 48 for the CD8+ subset. There existed some CR-exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRβ clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients.

Conclusion: Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRβ CDR3 motif may be utilized for CHB immunotherapy in the future.

Keywords: Chronic hepatitis B; Entecavir; Hepatitis B e antigen seroconversion; Immune response; T-cell receptor sequencing.

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StephenW

恩替卡韦治疗期间与乙型肝炎E抗原血清转化有关的不同T细胞受体谱
易一莲1，徐旭2，古玉容3，毕彦华1，廖春红1，赵苗贤2，廖夏莲1，王占辉2，吴宏凯4，黄月华1 3
隶属关系
隶属关系

    1个
    中山大学附属第三医院广东省肝病研究重点实验室，广州
    2
    南方医科大学附属南方医院传染病与肝病科，器官衰竭研究国家重点实验室，广东省病毒性肝炎研究重点实验室，广州。
    3
    中山大学附属第三医院传染病科，广州
    4
    广州医科大学附属第一医院，呼吸疾病国家重点实验室，国家呼吸疾病临床研究中心，广州。

    PMID：32564486 DOI：10.1111 / liv.14566

抽象

背景与目的：慢性乙型肝炎（CHB）患者在抗病毒治疗过程中T细胞受体（TCR）的组成存在歧义变化。我们试图评估CHR患者中TCR谱库动力学及其对HBeAg血清转化的临床意义。

方法：招募了20名接受1年恩替卡韦（ETV）治疗的CHB患者，包括第48周时基于HBeAg血清转化的10例完全缓解（CR）vs 10例非完全缓解（NCR）。TCRβ互补决定区3（通过无偏高通量测序分析第0、12和48周时外周CD4 +和CD8 + T细胞的CDR3）。分析了TCR库谱及其与血清学参数的相关性。

结果：CR患者的TCRβ库的多样性正在减少，而NCR患者则有所增加。根据CR型和NCR患者在相反方向上的克隆型频率分层的TCR库的分布模式。 CR患者中出现的少量新克隆型经历了更强烈，更强劲的扩张，这种现象最早可能在CD4 +亚组的第12周出现，而在CD8 +亚组的第48周以后出现。在第48周时，存在一些CR除外的克隆型，频率相对较低，但频率增加。CR患者中独特的TCRβ克隆型的数量与ALT或HBV DNA水平呈正相关，而在NCR患者中则没有或呈负相关。

结论：不同的TCR谱有助于在ETV治疗期间预测CHB患者的HBeAg血清转化，将来某些TCRβCDR3基序可用于CHB免疫治疗。

关键字：慢性乙型肝炎；恩替卡韦;乙型肝炎e抗原血清转化；免疫反应; T细胞受体测序。

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