乙型肝炎表面抗原對慢性乙型肝炎感染患者自然殺傷細胞的

StephenW

The impact of hepatitis B surface antigen on natural killer cells in patients with chronic hepatitis B infection
Yanqin Du  1 , Olympia E Anastasiou  2 , Benedikt Strunz  3 , Janina Scheuten  1 , Birgit Bremer  4 , Anke Kraft  4   5   6 , Karolina Kleinsimglinhaus  1 , Daniel Todt  7   8 , Ruth Broering  1 , Matthias Hardtke-Wolenski  1 , Jun Wu  9 , Dongliang Yang  9 , Ulf Dittmer  2 , Mengji Lu  2 , Markus Cornberg  4   5   10   6   11 , Niklas K Björkström  3 , Tanvi Khera  1   4 , Heiner Wedemeyer  1   4   10
Affiliations
Affiliations

    1
    Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
    2
    Institute for Virology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
    3
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    4
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
    5
    Center for individualized infection medicine (CIIM), Hannover, Germany.
    6
    Centre for Experimental and Clinical Infection Research, Hannover, Germany.
    7
    Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
    8
    European Virus Bioinformatics Center (EVBC), Jena, Germany.
    9
    Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    10
    German Center for Infection Research (DZIF), partner site Braunschweig, Germany.
    11
    Cluster of Excellence Resolving Infection Susceptibility (RESIST:EXC), Hannover Medical School, Hannover, Germany.

    PMID: 33794040 DOI: 10.1111/liv.14885

Abstract

Background & aims: During chronic hepatitis B virus (HBV) infection, suppressed functionality of natural killer (NK) cells might contribute to HBV persistence but the underlying mechanisms remain elusive. A peculiar feature of HBV is the secretion of large amount of hepatitis B surface antigen (HBsAg). However, the effect of HBsAg quantities on NK cells is unclear. The aim was to determine the effects of HBsAg quantities on NK cell functionality in patients with chronic hepatitis B (CHB).

Methods: 80 CHB patients were included and categorized into four groups based on their HBsAg levels. As a control, 30 healthy donors were enrolled. NK cell frequency, phenotype and function were assessed using flow cytometry and correlated with HBsAg levels and liver enzymes.

Results: Compared to the healthy controls, a reshaping of NK cell pool towards more CD56bright NK cells was observed during CHB infection. Importantly, NK cells in patients with low HBsAg levels (<100 IU/ml) displayed an activated phenotype with increased expression of activation makers CD38, Granzyme B and proliferation marker Ki-67 while presenting with defective functional responses (MIP-1β, CD107a) at the same time. Furthermore, NK cell activation was negatively correlated with patient HBsAg levels while NK function correlated with patient age.

Conclusions: The differential regulation of NK cell phenotype and function suggests that activation of NK cells in patients with low serum HBsAg levels may contribute to HBV clearance.

Keywords: hepatitis B; hepatitis B surface antigen; immune response; natural killer cells.

This article is protected by copyright. All rights reserved.

StephenW

乙型肝炎表面抗原對慢性乙型肝炎感染患者自然殺傷細胞的影響
杜延琴1，奧林匹亞E阿納斯塔西歐2，貝內迪克特·斯特倫茲3，珍妮娜·舒滕1，比爾吉特·布雷默4，安克·卡夫4 5 6，卡羅琳娜·克萊因西姆林豪斯1，丹尼爾·托特7 8，露絲·布羅林1，馬提亞斯·哈特克-沃倫斯基1，胡君9，楊東亮9，烏爾夫·迪特默2，孟吉路2，馬庫斯·康伯格4 5 10 6 11，尼古拉斯·比約克斯特羅姆3，坦維·凱拉1 4，海納·韋德邁爾1 4 10
隸屬關係
隸屬關係

    1個
    杜伊斯堡-埃森大學，德國埃森，埃森大學醫院消化內科和肝病科。
    2個
    德國埃森杜伊斯堡埃森大學埃森大學醫院病毒學研究所。
    3
    瑞典斯德哥爾摩卡羅林斯卡大學醫院卡羅林斯卡研究所醫學系Huddinge感染醫學中心。
    4
    德國漢諾威漢諾威醫學院胃腸病學，肝病學和內分泌學系。
    5
    德國漢諾威個人感染醫學中心（CIIM）。
    6
    德國漢諾威，實驗和臨床感染研究中心。
    7
    德國波鴻魯爾大學分子與醫學病毒學系。
    8
    歐洲病毒生物信息學中心（EVBC），德國耶拿。
    9
    華中科技大學同濟醫學院附屬協和醫院感染科，武漢。
    10
    德國感染研究中心（DZIF），合作夥伴站點，德國不倫瑞克。
    11
    德國漢諾威漢諾威醫學院，卓越的解決感染易感性集群（RESIST：EXC）。

    PMID：33794040 DOI：10.1111 / liv.14885

抽象的

背景與目的：在慢性乙型肝炎病毒（HBV）感染期間，抑制自然殺傷（NK）細胞的功能可能有助於HBV持久性，但其潛在機制仍然難以捉摸。 HBV的一個特殊特徵是分泌大量的乙型肝炎表面抗原（HBsAg）。但是，HBsAg量對NK細胞的影響尚不清楚。目的是確定HBsAg量對慢性乙型肝炎（CHB）患者NK細胞功能的影響。

方法：納入80例CHB患者，根據其HBsAg水平分為四組。作為對照，招募了30名健康捐獻者。使用流式細胞儀評估NK細胞的頻率，表型和功能，並將其與HBsAg水平和肝酶相關。

結果：與健康對照組相比，在CHB感染期間觀察到NK細胞池向更多CD56bright NK細胞的重塑。重要的是，低HBsAg水平（<100 IU / ml）的患者的NK細胞表現出活化的表型，並帶有活化因子CD38，粒酶B和增殖標記物Ki-67的表達增加，而功能反應卻不完善（MIP-1β，CD107a）同時。此外，NK細胞活化與患者HBsAg水平呈負相關，而NK功能與患者年齡呈負相關。

結論：NK細胞表型和功能的差異性調節提示低血清HBsAg患者的NK細胞活化可能有助於HBV清除。

關鍵字：乙型肝炎；乙型肝炎表面抗原；免疫反應;自然殺傷細胞。

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