在慢性乙型肝炎和低水平HBsAg患者中核苷类似物治疗后恢复循

StephenW

Int Immunopharmacol. 2018 Jul 4;62:59-66. doi: 10.1016/j.intimp.2018.06.043. [Epub ahead of print]
Recovery of circulating CD56dim NK cells and the balance of Th17/Treg after nucleoside analog therapy in patients with chronic hepatitis B and low levels of HBsAg.
Liu N1, Liu B1, Zhang L1, Li H1, Chen Z1, Luo A1, Chen M1, Peng M1, Yin W1, Ren H1, Hu P2.
Author information

1
    Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
2
    Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: [email protected].

Abstract
BACKGROUND AND AIMS:

Much evidence indicates that the soluble antigens secreted by hepatitis B virus (HBV) inhibit the function of the immune system. The aim of this study is to investigate, after treatment with nucleoside (acid) analogs (NAs) and the inhibition of viral replication, whether the immune systems of patients with a peripheral blood HBV-DNA level <1000 IU/mL, hepatitis B e antigen (HBeAg) disappearance, and a decrease in hepatitis B surface antigen (HBsAg) levels could be reconstructed.
METHODS:

The frequency and phenotype of circulating natural killer (NK) cells, dendritic cells (DCs), T-helper (Th) cells, regulatory T (Treg) cells, CD4+, CD8+ T cells, T follicular helper (Tfh) cells and B cells subtypes were tested by flow cytometry in chronic hepatitis B (CHB) patients and healthy controls (HCs). The levels of HBV-related serum HBsAg, HBeAg, HBV-DNA load, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.
RESULTS:

Regarding the innate immune system, an increased frequency of CD56dim NK cells was found in the therapeutic response (TR) group compared with that in the immune-active phase (IA) group. Additionally, regarding the adaptive immune system, the Th17/CD4+CD25+CD127dimTreg ratio was reduced in the TR group. Additionally, the frequency of CD40L+CXCR5+CD4+T cells and CD40+CD19+CD27+CD38+B cells was significantly higher than that of HCs, while that of PDL1+CD19+ B cells was lower. Furthermore, the frequencies of CTLA4+CD4+T cells and CTLA4+CD8+T cells in patients with CHB were significantly higher than those in HCs.
CONCLUSION:

After NA treatment and the inhibition of viral replication, circulating CD56dim NK cells and the balance of Th17/Treg can be recovered. Restoring circulating CD56dim NK cells and the Th17/Treg balance may help reduce HBsAg levels in patients.

Copyright © 2018 Elsevier B.V. All rights reserved.
KEYWORDS:

Hepatitis B virus; Natural killer cells; Nucleoside analogs; Regulatory T cells; T-helper cells

PMID:
    29990695
DOI:
    10.1016/j.intimp.2018.06.043

StephenW

Int Immunopharmacol。 2018年7月4日; 62：59-66。 doi：10.1016 / j.intimp.2018.06.043。 [提前打印]
在慢性乙型肝炎和低水平HBsAg患者中核苷类似物治疗后恢复循环CD56dim NK细胞和Th17 / Treg平衡。
Liu N1，Liu B1，Zhang L1，Li H1，Chen Z1，Luo A1，Chen M1，Peng M1，Yin W1，Ren H1，Hu P2。
作者信息

1
    重庆医科大学附属第二医院病毒性肝炎研究所传染病科，传染病分子生物学重点实验室，重庆，中国。
2
    重庆医科大学附属第二医院病毒性肝炎研究所传染病科，传染病分子生物学重点实验室，重庆，中国。电子地址：[email protected]。

抽象
背景和目的：

大量证据表明，乙型肝炎病毒（HBV）分泌的可溶性抗原可抑制免疫系统的功能。本研究的目的是研究用核苷（酸）类似物（NAs）治疗和抑制病毒复制后，外周血HBV-DNA水平<1000IU / mL，乙型肝炎患者的免疫系统抗原（HBeAg）消失，可以重建乙型肝炎表面抗原（HBsAg）水平的降低。
方法：

循环自然杀伤（NK）细胞，树突状细胞（DC），T辅助细胞（Th），调节性T（Treg）细胞，CD4 +，CD8 + T细胞，T滤泡辅助细胞（Tfh）和B细胞的频率和表型在慢性乙型肝炎（CHB）患者和健康对照（HC）中通过流式细胞术测试亚型。测定HBV相关血清HBsAg，HBeAg，HBV-DNA载量，丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平。
结果：

关于先天免疫系统，与免疫活性期（IA）组相比，在治疗反应（TR）组中发现CD56dim NK细胞的频率增加。另外，关于适应性免疫系统，TR组中Th17 / CD4 + CD25 + CD127dimTreg比率降低。此外，CD40L + CXCR5 + CD4 + T细胞和CD40 + CD19 + CD27 + CD38 + B细胞的频率显着高于HCs，而PDL1 + CD19 + B细胞的频率较低。此外，CHB患者CTLA4 + CD4 + T细胞和CTLA4 + CD8 + T细胞的频率显着高于HCs。
结论：

在NA处理和抑制病毒复制后，可以回收循环CD56dim NK细胞和Th17 / Treg的平衡。恢复循环CD56dim NK细胞和Th17 / Treg平衡可能有助于降低患者的HBsAg水平。

版权所有©2018 Elsevier B.V.保留所有权利。
关键词：

乙型肝炎病毒;自然杀手细胞;核苷类似物;调节性T细胞; T辅助细胞

结论：
    29990695
DOI：
    10.1016 / j.intimp.2018.06.043