• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Ghosh, A.
    Ayithan, N.
    Romani, S.
    Khanam, A.
    Tang, L.
    Kottilil, S.
    Poonia, B.
    Date
    2020
    Journal
    Scientific Reports
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1038/s41598-020-58870-2
    https://doi.org/10.1038/s41598-020-62445-6
    Abstract
    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).
    Keyword
    Hepatitis B, Chronic
    Hepatitis B Surface Antigens
    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/10713/12008
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-020-58870-2
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    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
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.