Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients
Date
2020Journal
Scientific ReportsPublisher
Nature ResearchType
Article
Metadata
Show full item recordAbstract
Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBslo) or >50,000 IU/ml (HBshi) using immunological assays (flow cytometry, ICS, ELISPOT). HBshi patients had significantly higher expression of inhibitory PD-1 on CD4+ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBslo patients had IFNγ+TNFα+ and IFNγ+ IL2+ CD4+ T cell responses respectively, in comparison to 33% and 13% of HBshi patients. Checkpoint blockade with αPD-1 improved HBV-specific CD4+ T cell function only in HBslo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet αPD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100 IU/ml compared to patients with HBsAg >5,000 IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4+ T cell responses, and augmentation by checkpoint blockade. Copyright 2020, The Author(s).Description
Supplementary Tables 1 and 2 are omitted from the Supplementary Information which accompanies this Article. Tables S1 and S2 appear in https://doi.org/10.1038/s41598-020-62445-6.Sponsors
This work was supported by funds from Arbutus Biopharma to Institute of Human Virology (SK, BP).Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078888665&doi=10.1038%2fs41598-020-58870-2&partnerID=40&md5=15a25cca67939d7440e09618c08e74cc; http://hdl.handle.net/10713/12008ae974a485f413a2113503eed53cd6c53
10.1038/s41598-020-58870-2
Scopus Count
Collections
Related articles
- Effects of Hepatitis B Surface Antigen on Virus-Specific and Global T Cells in Patients With Chronic Hepatitis B Virus infection.
- Authors: Le Bert N, Gill US, Hong M, Kunasegaran K, Tan DZM, Ahmad R, Cheng Y, Dutertre CA, Heinecke A, Rivino L, Tan A, Hansi NK, Zhang M, Xi S, Chong Y, Pflanz S, Newell EW, Kennedy PTF, Bertoletti A
- Issue date: 2020 Aug
- Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B.
- Authors: Le Bert N, Salimzadeh L, Gill US, Dutertre CA, Facchetti F, Tan A, Hung M, Novikov N, Lampertico P, Fletcher SP, Kennedy PTF, Bertoletti A
- Issue date: 2020 Jan
- Circulating PD-1(hi)CXCR5(+)CD4(+) T cells are associated with a decrease in hepatitis B surface antigen levels in patients with chronic hepatitis B who are receiving peginterferon-α therapy.
- Authors: Zhang L, Li H, Ren H, Hu P
- Issue date: 2018 Nov
- Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.
- Authors: Dammermann W, Bentzien F, Stiel EM, Kühne C, Ullrich S, Schulze Zur Wiesch J, Lüth S
- Issue date: 2015 May 13
- Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients.
- Authors: Vyas AK, Sharma BC, Sarin SK, Trehanpati N
- Issue date: 2018 Jan