HBV準種特徵對HBV C基因型HBsAg+/HBsAb+患者免疫狀態的影響使用

StephenW

HBV準種特徵對HBV C基因型HBsAg+/HBsAb+患者免疫狀態的影響使用下一代測序
王英1、肖曉1 2、陳世鵬1、黃陳軍1、周軍1、戴二黑3、亞麗4、劉麗娟5、黃憲章6、高致遠1 2、吳傳勇2、孟芳1、春芳高 1 2
隸屬關係
隸屬關係

    1
    上海東方肝膽外科醫院檢驗科，上海，中國。
    2
    【作者單位】： 上海中醫藥大學岳陽中西醫結合醫院臨床檢驗醫學中心;
    3
    河北醫科大學石家莊第五醫院檢驗科，中國石家莊。
    4
    昆明醫科大學第一附屬醫院檢驗科，昆明，中國。
    5
    福建醫科大學孟超肝膽醫院檢驗科，中國福州
    6
    廣州中醫藥大學第二附屬醫院檢驗科，廣州，中國。

    PMID：34899733 PMCID：PMC8656693 DOI：10.3389/fimmu.2021.775461

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背景：本研究旨在通過對慢性乙型肝炎 (CHB) 和肝細胞癌中 HBV s 基因的深入表徵，探討乙型肝炎表面抗原 (HBsAg) 和乙型肝炎表面抗體 (HBsAb) 血清學模式共存的分子機制。 HCC) 患者。

方法：共納入來自中國13個醫療中心的73例HBsAg+/HBsAb+患者（CHB=36，HCC=37）和96例HBsAg+/HBsAb-患者（CHB=47，HCC=49）。基於二代測序（NGS）和多維生物信息學分析相結合，闡述了序列特徵。

結果：16個高頻錯義突變、終止密碼子突變的變化、聚類和基於準種特徵的隨機森林模型分別證明了HBsAg+/HBsAb+和HBsAg+/HBsAb-在CHB和HCC中的顯著差異能力。 HBsAg+/HBsAb+ 患者的細胞毒性 T 淋巴細胞 (CTL) 表位 Se 的免疫原性和主要親水區 (MHR) 的抗原性均降低（CTL Se：p < 0.0001；MHR：p = 0.0216）。在患有 CHB 和患有 HCC 的 HBsAg+/HBsAb+ 患者之間觀察到不同的突變模式。特別是，抗原表位的突變，如 CHB 中的 I126S 和 HCC 中的 I126T，可能會影響構象結構並改變 HBsAg 的抗原性/免疫原性。

結論：基於NGS和生物信息學分析，本研究首次表明HBV s基因的點突變和準種多樣性可以改變MHR抗原性和CTL Se免疫原性，並可能導致HCC和HCC並發不同特徵的HBsAg+/HBsAb+慢性乙型肝炎。我們的發現可能會更新對這種特殊血清學特徵的理解，並有益於 HBV 相關疾病的臨床管理。

關鍵詞：乙肝表面抗體（HBsAb）；乙型肝炎表面抗原（HBsAg）；乙型肝炎病毒（HBV）；下一代測序（NGS）；準種。

版權所有 © 2021 Wang, Xiao, Chen, Huang, Zhou, Dai, Li, Liu, Huang, Gao, Wu, Fang and Gao.

StephenW

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
Ying Wang  1 , Xiao Xiao  1   2 , Shipeng Chen  1 , Chenjun Huang  1 , Jun Zhou  1 , Erhei Dai  3 , Ya Li  4 , Lijuan Liu  5 , Xianzhang Huang  6 , Zhiyuan Gao  1   2 , Chuanyong Wu  2 , Meng Fang  1 , Chunfang Gao  1   2
Affiliations
Affiliations

    1
    Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
    2
    Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
    3
    Department of Laboratory Medicine, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, China.
    4
    Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
    5
    Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.
    6
    Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

    PMID: 34899733 PMCID: PMC8656693 DOI: 10.3389/fimmu.2021.775461

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Abstract

Background: This study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.

Method: A total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb- patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis.

Results: The 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb- in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg.

Conclusion: Based on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.

Keywords: hepatitis B surface antibody (HBsAb); hepatitis B surface antigen (HBsAg); hepatitis B virus (HBV); next-generation sequencing (NGS); quasispecies.

Copyright © 2021 Wang, Xiao, Chen, Huang, Zhou, Dai, Li, Liu, Huang, Gao, Wu, Fang and Gao.

StephenW

https://www.frontiersin.org/arti ... mmu.2021.775461/pdf