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标题: 乙型肝炎表面抗原自发性血清学转换在乙型肝炎e抗原阴性慢 [打印本页]

作者: StephenW 时间: 2017-12-23 08:04 标题: 乙型肝炎表面抗原自发性血清学转换在乙型肝炎e抗原阴性慢

Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients

Ashish Kumar Vyas1, Barjesh Chander Sharma2, Shiv Kumar Sarin2,* andNirupma Trehanpati1,*

Version of Record online: 1 JUN 2017

DOI: 10.1111/liv.13475

© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Liver International

Volume 38, Issue 1, pages 38–49, January 2018
Article has an altmetric score of 2

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

Email: Shiv Kumar Sarin ([email protected]), Nirupma Trehanpati ([email protected])

* Correspondence
Nirupma Trehanpati and Shiv Kumar Sarin, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India.
Emails: [email protected] and [email protected]

Keywords:

HBsAg seroconversion;HBV infection;IL-21;T follicular helper cells;toll like receptors

Abstract
Background

Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg −ve chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired humoral response. We investigated the role of dendritic cells (DCs), T follicular helper (TFH) cells and plasma B cells in seroconversion.
Methods

HBeAg −ve (n=135) CHB patients with raised ALT at baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11) were compared with non-converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes (TFH, B and DCs), HBV specific T-cell functionality [using pooled overlapping surface and core peptides], IL21 levels and gene expression analysis by qRT-PCR.
Results

Patients in Gr. I compared to Gr. II and III, had higher IL-21 levels (865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4+CXCR5+) cells (12.3 vs 4.67 vs 2.77, P=<.001), inducible T-cell co-stimulator (ICOS) expression on TFH cells (20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL-17 (9.40 vs 2.33 vs 2.61, P=<.001) and TNF-α secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001), plasma B (CD19+CD38+) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs 5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001). Plasma B-cell frequency (R2=.64, P=.01) and IL-21 levels (R2=.52, P=.003) correlated with anti-HBs titres in patients with HBsAg seroconversion.
Conclusions

Dendritic cell and TFH cell mediated responses regulate humoral responses against HBV and play a major role in HBsAg seroconversion in CHB patients.

作者: StephenW 时间: 2017-12-23 08:04

乙型肝炎表面抗原自发性血清学转换在乙型肝炎e抗原阴性慢性乙型肝炎患者中的免疫相关性

Ashish Kumar Vyas1，Barjesh Chander Sharma2，Shiv Kumar Sarin2，*和Nirupma Trehanpati1，*

在线记录版本：2017年6月1日

DOI：10.1111 / liv.13475

©2017 John Wiley＆Sons A / S。 John Wiley＆Sons Ltd出版

肝脏国际

卷38，第1期，第38-49页，2018年1月
文章的对等分数为2

1印度新德里肝胆科学研究所分子和细胞医学系
2印度新德里肝胆科学研究所肝病研究所

电子邮件：Shiv Kumar沙林（[email protected]），Nirupma Trehanpati（[email protected]）

*通信
Nirupma Trehanpati和Shiv Kumar Sarin，印度新德里肝胆研究所（ILBS）。
电子邮件：[email protected]和[email protected]

关键词：

HBsAg血清学转换; HBV感染; IL-21; T滤泡辅助细胞; toll样受体

抽象
背景

HBeAg阳性的乙型肝炎表面抗原（HBsAg）血清转换非常罕见，可能是由于抗原加工不良和体液应答受损。我们研究了树突状细胞（DC），T滤泡辅助细胞（TFH）和血浆B细胞在血清转化中的作用。
方法

HBeAg -ve（n = 135）CHB患者基线ALT升高随访。（Gr。II，n = 17，HBV DNA <2000 IU / mL）或高HBV DNA（Gr。III，HBV DNA> 11）的非转化者进行HBsAg血清学转换的患者2000 IU / mL，n = 17）。我们使用qRT-PCR测量细胞表型（TFH，B和DC），HBV特异性T细胞功能[使用汇集的重叠表面和核心肽]，IL21水平和基因表达分析。
结果

Gr。我比较Gr。 II和III型患者IL-21水平较高（分别为865 vs 276 vs 111 pg / mL，P = <0001），TFH（CD4 + CXCR5 +）细胞（12.3 vs 4.67 vs 2.77，P = <0.001）（20.0vs13.0vs13.68，P = 0.01），HBsAg特异性IL-17（9.40vs2.33vs2.61，P = <0.001）和TNF-α分泌TFH17细胞的细胞共刺激因子（ICOS）（分别为82 vs 1.43 vs 2.33，P = <0.001），血浆B（CD19 + CD38 +）细胞（15.0 vs 5.08 vs 5.57，P = <0.001），髓样（17.80 vs 5.39 vs 2.70，P = <0.001）和浆细胞样DC（2.6比0.43比0.21，P = <0.001）。血浆B细胞频率（R2 = .64，P = .01）和IL-21水平（R2 = .52，P = .003）与HBsAg血清转换患者的抗-HBs滴度相关。
结论

树突状细胞和TFH细胞介导的应答调节针对HBV的体液应答，并且在CHB患者中的HBsAg血清转化中起主要作用。

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