PMID- 34702717
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221102
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Print)
IS  - 0017-5749 (Linking)
VI  - 71
IP  - 11
DP  - 2022 Nov
TI  - Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T 
      cells in patients with chronic hepatitis B virus infection.
PG  - 2300-2312
LID - 10.1136/gutjnl-2021-324646 [doi]
AB  - OBJECTIVE: Hepatitis B virus (HBV)-specific T cells are main effector cells in 
      the control of HBV infection and hepatitis B surface antigen (HBsAg) is suggested 
      to be a critical factor in the impaired immune response, a hallmark of chronic 
      HBV infection. In addition to HBsAg, other viral markers such as hepatitis B 
      core-related antigen (HBcrAg) are available, but their potential association with 
      HBV-specific immune responses is not defined yet, which will be important if 
      these markers are used for patient stratification for novel therapies aimed at 
      functional HBV cure. DESIGN: We analysed T cell responses in 92 patients with 
      hepatitis B e antigen negative chronic HBV infection with different HBsAg and 
      HBcrAg levels. Overlapping peptides were used for in vitro response analyses 
      (n=57), and HBV core(18)-specific and polymerase (pol)(455)-specific CD8(+) T 
      cells were assessed in human leukocyte antigen (HLA)-A*02 patients (n=35). In 
      addition, in vitro responsiveness to anti-programmed cell death-ligand 1 
      (anti-PD-L1) was investigated. RESULTS: HBV-specific T cell responses were not 
      affected by HBsAg levels, but rather by age and CD4(+) T cell responses were 
      highest in patients with low HBcrAg levels. The phenotypes and functionality of 
      HBV core(18)-specific and pol(455)-specific CD8(+) T cells differed, but HBsAg 
      and HBcrAg levels did not affect their profiles. Blocking with anti-PD-L1 could 
      restore HBV-specific T cells, but the effect was significantly higher in T cells 
      isolated from patients with low HBsAg and in particular low HBcrAg. CONCLUSION: 
      Our data suggest that age and HBcrAg rather than HBsAg, are associated with 
      HBV-specific T cell responses. Finally, very low antigen levels indicated by 
      HBsAg and in particular HBcrAg may influence T cell response to checkpoint 
      inhibition.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Aliabadi, Elmira
AU  - Aliabadi E
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
FAU - Urbanek-Quaing, Melanie
AU  - Urbanek-Quaing M
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
FAU - Maasoumy, Benjamin
AU  - Maasoumy B
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
FAU - Bremer, Birgit
AU  - Bremer B
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
FAU - Grasshoff, Martin
AU  - Grasshoff M
AD  - Computational Biology for Individualised Medicine, Helmholtz Centre for Infection 
      Research (HZI), c/o CRC, Hannover, Germany.
FAU - Li, Yang
AU  - Li Y
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
AD  - Computational Biology for Individualised Medicine, Helmholtz Centre for Infection 
      Research (HZI), c/o CRC, Hannover, Germany.
AD  - Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany.
FAU - Niehaus, Christian E
AU  - Niehaus CE
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
FAU - Wedemeyer, Heiner
AU  - Wedemeyer H
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
FAU - Kraft, Anke R M
AU  - Kraft ARM
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany.
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
FAU - Cornberg, Markus
AU  - Cornberg M
AUID- ORCID: 0000-0002-9141-8001
AD  - Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical 
      School, Hannover, Germany cornberg.markus@mh-hannover.de.
AD  - TWINCORE Center of Experimental and Clinical Infection Research, Hannover, 
      Germany.
AD  - German Centre for Infection Research (Deutsches Zentrum fur Infektionsforschung 
      DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
AD  - Centre for Individualized Infection Medicine (CiiM), c/o CRC, Hannover, Germany.
AD  - Cluster of Excellence Resolving Infection Susceptibility (RESIST; EXC 2155), 
      Hannover Medical School, Hannover, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Biomarkers)
RN  - 0 (DNA, Viral)
RN  - 0 (HLA Antigens)
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Hepatitis B e Antigens)
SB  - IM
CIN - Gut. 2022 Nov;71(11):2149-2151. PMID: 34799373
MH  - Biomarkers
MH  - CD8-Positive T-Lymphocytes
MH  - DNA, Viral/analysis
MH  - HLA Antigens
MH  - *Hepatitis B
MH  - Hepatitis B Core Antigens
MH  - Hepatitis B Surface Antigens
MH  - Hepatitis B e Antigens
MH  - Hepatitis B virus/genetics
MH  - *Hepatitis B, Chronic/drug therapy
MH  - Humans
MH  - Phenotype
PMC - PMC9554084
OTO - NOTNLM
OT  - T lymphocytes
OT  - cellular immunology
OT  - chronic hepatitis
OT  - hepatitis B
OT  - immune response
COIS- Competing interests: None declared.
EDAT- 2021/10/28 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/10/12
CRDT- 2021/10/27 06:12
PHST- 2021/03/12 00:00 [received]
PHST- 2021/10/05 00:00 [accepted]
PHST- 2021/10/28 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2021/10/27 06:12 [entrez]
PHST- 2022/10/12 00:00 [pmc-release]
AID - gutjnl-2021-324646 [pii]
AID - 10.1136/gutjnl-2021-324646 [doi]
PST - ppublish
SO  - Gut. 2022 Nov;71(11):2300-2312. doi: 10.1136/gutjnl-2021-324646. Epub 2021 Oct 
      26.