Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8503886 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0641 (Electronic) Linking ISSN: 01688278 NLM ISO Abbreviation: J Hepatol Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Amsterdam : Elsevier
      Original Publication: Copehnagen : Munksgaard International Publishers, [c1984-
    • Subject Terms:
      Hepatitis B, Chronic*/drug therapy ; Hepatitis B, Chronic*/immunology ; Interferon-alpha*/therapeutic use ; Antiviral Agents*/therapeutic use ; Hepatitis B Surface Antigens*/immunology ; Hepatitis B Surface Antigens*/blood ; Polyethylene Glycols*/therapeutic use ; Polyethylene Glycols*/administration & dosage; Humans ; Male ; Female ; Adult ; Middle Aged ; Recombinant Proteins/therapeutic use ; Recombinant Proteins/administration & dosage ; B-Lymphocytes/immunology ; B-Lymphocytes/drug effects ; Hepatitis B virus/immunology ; ADP-ribosyl Cyclase 1/immunology ; Receptors, CXCR3 ; Hepatitis B Core Antigens/immunology ; Memory B Cells/immunology ; Immunoglobulin G
    • Abstract:
      Background & Aims: The changes in HBV-specific B cells in patients with chronic hepatitis B (CHB) undergoing pegylated interferon-α (PEG-IFNα) treatment and achieving functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B cells.
      Methods: We included 39 nucleos(t)ide analogue-treated patients with CHB who received sequential combination therapy with PEG-IFNα and eight treatment-naïve patients. HBV-specific B cells were characterized ex vivo using fluorescently labeled hepatitis B surface and core antigens (HBsAg and HBcAg). The frequency, phenotype, and subsets of HBV-specific B cells and follicular helper T cells (Tfh cells) were detected using flow cytometry. The functionality of HBV-specific B cells was quantified through ELISpot assays.
      Results: During treatment, the fraction of activated memory B cells (MBCs) among HBsAg-specific B cells and the expression of IgG, CXCR3, and CD38 increased. The antibody-secretion capacity of HBsAg-specific B cells was only restored in patients achieving a functional cure after treatment and it positively correlated with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG + classical MBCs and plasmablasts among HBsAg-specific B cells. HBcAg-specific B cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM + atypical type of MBC after treatment, irrespective of functional cure. The number of CD40L + Tfh cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation.
      Conclusions: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L + Tfh cells is associated with the active recovery of HBsAg-specific B cells.
      Impact and Implications: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of patients with chronic hepatitis B offers a promising therapeutic strategy for viral clearance, e.g. via therapeutic vaccination. We analyzed the alterations in HBV-specific B cells in patients treated with pegylated interferon-α and identified novel pathways for immunotherapeutic boosting of B cell immunity.
      (Copyright © 2024. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Chronic hepatitis B; HBV-specific B cells; HBsAg; Immune response; Interferon
    • Accession Number:
      0 (Interferon-alpha)
      0 (Antiviral Agents)
      0 (Hepatitis B Surface Antigens)
      3WJQ0SDW1A (Polyethylene Glycols)
      0 (Recombinant Proteins)
      Q46947FE7K (peginterferon alfa-2a)
      EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
      0 (Receptors, CXCR3)
      0 (CXCR3 protein, human)
      0 (Hepatitis B Core Antigens)
      0 (Immunoglobulin G)
    • Publication Date:
      Date Created: 20240711 Date Completed: 20241117 Latest Revision: 20241117
    • Publication Date:
      20241118
    • Accession Number:
      10.1016/j.jhep.2024.06.033
    • Accession Number:
      38992769