Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Issue 11 (26th October 2021)

• Record Type: Journal Article
• Authors: Aliabadi, Elmira; Urbanek-Quaing, Melanie; Maasoumy, Benjamin; Bremer, Birgit; Grasshoff, Martin; Li, Yang; Niehaus, Christian E; Wedemeyer, Heiner; Kraft, Anke R M; Cornberg, Markus
• Is Part Of: Gut. Volume 71:Issue 11(2022)
• Page Start: 2300
• Page End: 2312
• Publication Date: 2021-10-26
• Subjects: hepatitis B -- cellular immunology -- chronic hepatitis -- immune response -- T lymphocytes; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2021-324646
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : 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 core18 -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 core18 -specific and pol455 -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.