CTL相关和NK细胞相关的免疫应答在慢性乙型肝炎患者中诱导不

StephenW

J Viral Hepat. 2018 Jul 11. doi: 10.1111/jvh.12970. [Epub ahead of print]
CTL-associated and NK cell-associated immune responses induce different HBV DNA reduction patterns in chronic hepatitis B patients.
Nomura M1,2, Tsuge M1,2,3, Uchida T1,2, Hiraga N1,2, Kurihara M1,2, Tsushima K1,2, Fujino H1,2, Nakahara T1,2, Murakami E1,2, Abe-Chayama H2,4, Kawaoka T1,2, Miki D1,2,5, Hiramatsu A1,2, Imamura M1,2, Kawakami Y1,2, Aikata H1,2, Ochi H1,2,5, Zhang Y1,2, Makokha GN1,2, Hayes CN1,2, Tanaka S1,6, Chayama K1,2,5.
Author information

1
    Department of Gastroenterology and Metabolism, Division of Frontier Medical Science, Programs for Biomedical Research Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan.
2
    Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
3
    Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
4
    Center for Medical Specialist Graduate Education and Research, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
5
    Laboratory for Digestive Diseases, RIKEN Center for Integrative Medical Sciences, Hiroshima, Japan.
6
    Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.

Abstract

The activation of hepatitis B virus (HBV)-related hepatitis is associated with both natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). We analyzed the association between the immune response and changes in the proportion of Pre-S deletion variants. We quantified Pre-S deleted HBV (HBV-del) and wild type HBV (HBV-wt) DNA levels in sera obtained from HBV-infected mice and chronic hepatitis B patients. In chronic hepatitis B patients, the HBV-del proportion usually increased during or after ALT elevation but did not occur during all ALT elevations. To clarify this difference in the immunological responses, we performed in vivo analyses using HBV-infected human hepatocyte chimeric mice. Although HBV-del proportions did not change in mice with NK cell-associated hepatitis or in mice treated with entecavir, the proportions sharply increased in mice with CTL-associated hepatitis. Furthermore, the number of patients in which HBV-del proportions were greater than 5% was significantly higher in chronic hepatitis B patients than in asymptomatic carriers (P=0.023). We identified associations between virological response in chronic hepatitis B patients and two different immune responses. The proportion of HBV-del variants could be a useful biomarker for distinguishing between chronic hepatitis and asymptomatic carriers. This article is protected by copyright. All rights reserved.
KEYWORDS:

HBV ; HBV DNA reduction; Pre-S deletion; hepatitis; immune response

PMID:
    29998562
DOI:
    10.1111/jvh.12970

StephenW

J病毒肝病。 2018年7月11日doi：10.1111 / jvh.12970。 [提前打印]
CTL相关和NK细胞相关的免疫应答在慢性乙型肝炎患者中诱导不同的HBV DNA减少模式。
野村M1,2，Tsuge M1,2,3，Uchida T1,2，Hiraga N1,2，Kurihara M1,2，Tsushima K1,2，Fujino H1,2，中原T1,2，村上E1,2，Abe-Chayama H2,4，Kawaoka T1,2，Miki D1,2,5，Hiramatsu A1,2，Imamura M1,2，Kawakami Y1,2，Aikata H1,2，Ochi H1,2,5，Zhang Y1,2，Makokha GN1 ，2，Hayes CN1,2，Tanaka S1,6，Chayama K1,2,5。
作者信息

1
    日本广岛大学广岛大学生物医学研究生物医学研究所生物医学研究项目，消化内科和代谢科。
2
    广岛大学肝脏研究项目中心，日本广岛。
3
    广岛大学自然科学基础研究开发中心，日本广岛。
4
    日本广岛，广岛大学生物医学与健康科学研究所医学专家研究生教育研究中心。
五
    消化疾病实验室，RIKEN综合医学中心，日本广岛。
6
    日本广岛县广岛大学医院内窥镜科。

抽象

乙型肝炎病毒（HBV）相关性肝炎的激活与自然杀伤（NK）细胞和细胞毒性T淋巴细胞（CTL）相关。我们分析了免疫应答与Pre-S缺失变体比例变化之间的关联。我们量化了从HBV感染的小鼠和慢性乙型肝炎患者获得的血清中的Pre-S缺失的HBV（HBV-del）和野生型HBV（HBV-wt）DNA水平。在慢性乙型肝炎患者中，HBV-del比例通常在ALT升高期间或之后增加，但在所有ALT升高期间均未发生。为了阐明免疫应答中的这种差异，我们使用HBV感染的人肝细胞嵌合小鼠进行体内分析。虽然HBV-del比例在NK细胞相关性肝炎小鼠或用恩替卡韦治疗的小鼠中没有变化，但CTL相关性肝炎小鼠的比例急剧增加。此外，HBV-del比例大于5％的患者数量在慢性乙型肝炎患者中显着高于无症状携带者（P = 0.023）。我们确定了慢性乙型肝炎患者的病毒学应答与两种不同的免疫应答之间的关联。 HBV-del变体的比例可能是区分慢性肝炎和无症状携带者的有用生物标志物。本文受版权保护。版权所有。
关键词：

HBV; HBV DNA减少; Pre-S删除;肝炎;免疫反应

结论：
    29998562
DOI：
    10.1111 / jvh.12970