在乙型肝炎e抗原阴性的慢性乙型肝炎患者乙型肝炎表面抗原

StephenW

Liver Int. 2017 May 13. doi: 10.1111/liv.13475. [Epub ahead of print]
Immune Correlates of Hepatitis B surface antigen spontaneous seroconversion in Hepatitis B e Antigen negative chronic hepatitis B patients.
Vyas AK1, Sharma BC2, Sarin SK2, Trehanpati N1.
Author information

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.

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 sero-conversion (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 >2,000 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=<0.0001), TFH (CD4+CXCR5+) cells (12.3 vs. 4.67 vs. 2.77, p=<0.001), inducible T-cell co-stimulator (ICOS) expression on TFH cells (20.0 vs. 13.0 vs. 13.68, p=0.01), HBsAg specific IL-17 (9.40 vs. 2.33 vs.2.61, p=<0.001) and TNF-α secreting TFH17 cells (82 vs. 1.43 vs. 2.33, p=<0.001), plasma B (CD19+CD38+) cells (15.0 vs. 5.08 vs. 5.57 p=<0.001), myeloid (17.80 vs. 5.39 vs. 2.70 p=<0.001) and plasmocytoid DCs (2.6 vs. 0.43 vs. 0.21 p=<0.001). Plasma B cell frequency (R2 =0.64 P=0.01) and IL-21 levels (R2 =0.52, P=0.003) correlated with anti-HBs titers 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. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HBV infection; HBsAg seroconversion; IL-21; T follicular helper cells; Toll Like receptors

PMID:
    28500636
DOI:
    10.1111/liv.13475

StephenW

肝脏内2017年5月13日。doi：10.1111 / liv.13475。 [提前印刷]
在乙型肝炎e抗原阴性的慢性乙型肝炎患者乙型肝炎表面抗原的血清转换自发免疫相关因素。
Vyas AK1，Sharma BC2，Sarin SK2，Trehanpati N1。
作者信息

1印度新德里肝胆外科研究所分子与细胞医学系。
2印度新德里肝胆外科研究所肝脏病学系。

抽象
背景：

HBeAg-ve慢性乙型肝炎（CHB）感染中的乙型肝炎表面抗原（HBsAg）血清学转换是罕见的，可能是由于抗原加工不良和体液反应受损。我们研究了树突状细胞（DCs），T滤泡辅助细胞（TFH）细胞和血浆B细胞在血清转化中的作用。
方法：

随访时，HBeAg-ve（n = 135）CHB患者ALT升高。将经历HBsAg血清转化的患者（Gr.1，n = 11）与低转化率（Gr II，n = 17，HBV DNA <2000IU / ml）或高HBV DNA（Gr.3，HBV DNA> 2,000IU / ml，n = 17）。我们通过qRT-PCR测量细胞表型（TFH，B和DCs），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：

患者在Gr。我比较了Gr。 II和III具有较高的IL-21水平（865对比276 vs.111pg / mL，p = <0.0001），TFH（CD4 + CXCR5 +）细胞（12.3对4.67对2.77，p = <0.001）在TFH细胞上的诱导型T细胞共刺激因子（ICOS）表达（20.0 vs. 13.0对比13.68，p = 0.01），HBsAg特异性IL-17（9.40对2.33对比2.61，p = <0.001） α分泌TFH17细胞（82对1.43对2.33，p = <0.001），血浆B（CD19 + CD38 +）细胞（15.0对5.08对5.57 p = <0.001），骨髓（17.80对5.39 vs. 2.70 p = <0.001）和浆细胞DC（2.6 vs. 0.43对0.21 p = <0.001）。血浆B细胞频率（R2 = 0.64 P = 0.01）和IL-21水平（R2 = 0.52，P = 0.003）与HBsAg血清学转换患者的抗HBs滴度相关。
结论：

树突细胞和TFH细胞介导的应答调节对HBV的体液应答，并在CHB患者的HBsAg血清学转换中起主要作用。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

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

结论：
    28500636
DOI：
    10.1111 / liv.13475