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.
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。