乙型肝炎再激活患者乙型肝炎表面抗原血清学转换的免疫预

StephenW

乙型肝炎再激活患者乙型肝炎表面抗原血清学转换的免疫预测因子
Mojahidul Islam 1、Jayesh Kumar Sevak 1、Manoj Kumar Sharma 2、Ankur Jindal 2、Ashish Kumar Vyas 1、Meenu Bajpai 3、Gayatri Ramakrishna 1、Shiv Kumar Sarin 2、Nirupma Trehanpati 1
隶属关系
隶属关系

    1个
    分子和细胞医学系，肝脏和胆道科学研究所，新德里，印度。
    2个
    印度新德里肝脏与胆道科学研究所肝病学系。
    3个
    印度新德里肝脏与胆道科学研究所输血医学系。

    PMID：36411952 DOI：10.1111/apt.17306

抽象的

背景：乙型肝炎表面抗原 (HBsAg) 血清转化有时在乙型肝炎再激活 (rHBV) 中观察到，这可能是由于免疫重置和分化。

目的：研究实现 HBsAg 血清转化的 rHBV 患者的序贯免疫分化和耐受性消除。

方法：我们纳入了 19 名慢性乙型肝炎患者（CHBV；HBV DNA log103-8）、67 名 rHBV（ALT 升高 [>5XULN]、HBV DNAlog104-8）和 10 名健康对照。在基线和 24 周时评估 CD4、CD8、T 调节细胞 (Treg)、B 细胞和滤泡 T 辅助细胞 (Tfh) 的免疫分化、耐受性和功能状态。

结果：在 24 周时，81% 的 rHBV (n = 67) 失去了 HBV DNA 和 HBeAg (41%)，12 (19%) 失去了 HBsAg 并且抗-HBs 滴度 >10 IU/ml。 rHBV 患者具有较高的 Th1/17、TEM、Tfh、Tfh1/17、血浆和 ATM B 细胞，以及较低的 Tregs、Th2、Th17 和 TEMRA 表达。与 CHBV 相比，rHBV 显示出较低的 PD1、TIM3、LAG3、SLAM 和 TOX。与非血清转化者相比，血清转化者中的 CD8、CD8EM、Tfh、Tfh1/17 和血浆 B 细胞显着增加。在 24 周时，我们还观察到血清转化者的血浆 B 细胞频率增加。虽然非血清转化者在 CD4/CD8 T 细胞上显示出更高的 PD1、TIM3、LAG3、SLAM 和 TOX 表达，但阻断 PD1、TIM3、LAG3 和 CTLA4 显着增强了 IFN-γ、TNF-α、IL-4 和 IL-21在非血清转化者的 CD4/CD8 和 Tfh 细胞上表达。

结论：非血清转化者增加了 CD4/CD8 T 细胞的抑制标志物。 CD8、Tfh 和 B 细胞及其亚群在血清清除中发挥着关键作用，连同检查点分子作为 HBV 感染中非血清转化者的潜在疗法。

关键词：HBV免疫学； HBsAg 血清转化；慢性乙型肝炎；乙型肝炎病毒;乙肝病毒再激活；血清转化。

© 2022 John Wiley & Sons Ltd.

StephenW

Immune predictors of hepatitis B surface antigen seroconversion in patients with hepatitis B reactivation
Mojahidul Islam  1 , Jayesh Kumar Sevak  1 , Manoj Kumar Sharma  2 , Ankur Jindal  2 , Ashish Kumar Vyas  1 , Meenu Bajpai  3 , Gayatri Ramakrishna  1 , Shiv Kumar Sarin  2 , Nirupma Trehanpati  1
Affiliations
Affiliations

    1
    Departments of Molecular and Cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.
    2
    Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.
    3
    Department of Transfusion Medicine, Institute of Liver & Biliary Sciences, New Delhi, India.

    PMID: 36411952 DOI: 10.1111/apt.17306

Abstract

Background: Hepatitis B surface antigen (HBsAg) seroconversion is sometimes observed in hepatitis B reactivation (rHBV), probably due to immune resetting and differentiation.

Aims: To investigate sequential immune differentiation and abrogation of tolerance in patients with rHBV who achieved HBsAg seroconversion.

Methods: We included 19 patients with chronic hepatitis B (CHBV; HBV DNA log103-8 ), 67 with rHBV (raised ALT [>5XULN], HBV DNAlog104-8 ) and 10 healthy controls. Immune differentiation, tolerance and functional status of CD4, CD8, T regulatory cells (Tregs), B cells and follicular T helper (Tfh) cells were assessed at baseline and 24 weeks.

Results: At 24 weeks, 81% rHBV (n = 67) lost HBV DNA and HBeAg (41%), and 12 (19%) lost HBsAg and made anti-HBs titers >10 IU/ml. rHBV patients had higher Th1/17, TEM , Tfh, Tfh1/17, plasma and ATM B cells, and lower Tregs, Th2, Th17 and TEMRA expression. rHBV showed lower PD1, TIM3, LAG3, SLAM and TOX compared to CHBV. There was a significant increase in CD8, CD8EM, Tfh, Tfh1/17 and plasma B cells in seroconverters than non-seroconverters. At 24 weeks, we also observed increased plasma B cell frequency in seroconverters. While non-seroconverters showed higher expression of PD1, TIM3, LAG3, SLAM and TOX on CD4/CD8 T cells, blockade of PD1, TIM3, LAG3 and CTLA4 significantly enhanced IFN-γ, TNF-α, IL-4 and IL-21 expression on CD4/CD8 and Tfh cells in non-seroconverters.

Conclusions: Non-seroconverters have increased inhibitory markers on CD4/CD8 T cells. There is a critical play of CD8, Tfh and B cells and subsets in seroclearance, along with checkpoint molecules as a potential therapy for non-seroconverters in HBV infection.

Keywords: HBV immunology; HBsAg seroconversion; chronic hepatitis B; hepatitis B virus; reactivation of HBV; seroconversion.

© 2022 John Wiley & Sons Ltd.