B-Cell Activation Gene Signature in Blood and Liver of Hepatitis B e Antigen-Positive Patients With Immune Active Chronic Hepatitis B

Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into t...

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Bibliographic Details
Published in:The Journal of infectious diseases 2024-12, Vol.230 (6), p.e1263-e1273
Main Authors: Osmani, Zgjim, Beudeker, Boris J B, Groothuismink, Zwier M A, de Knegt, Robert J, Chung, Raymond T, Aerssens, Jeroen, Bollekens, Jacques, Janssen, Harry L A, Gehring, Adam J, Lauer, Georg M, Shalek, Alex K, van de Werken, Harmen J G, Boonstra, Andre
Format: Article
Language:English
Subjects:
Adult
B-Lymphocytes - immunology
Female
Gene Expression Profiling
Hepatitis B e Antigens - blood
Hepatitis B e Antigens - immunology
Hepatitis B virus - genetics
Hepatitis B virus - immunology
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - immunology
Hepatitis B, Chronic - virology
Humans
Liver - immunology
Liver - virology
Lymphocyte Activation - immunology
Major
Male
Middle Aged
Transcriptome
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Summary:Studies on chronic hepatitis B virus (HBV) infection have shown immune dysfunction involving multiple cell types, including T cells. B cells have been evaluated more recently, but in contrast to T cells, more pronounced activation of circulating B cells has been reported. To gain more insight into the activation status of B cells, we investigated gene profiles of B cells in the blood and liver of patients with chronic HBV. RNA-sequencing and flow cytometric analysis was performed on peripheral blood B cells of patients with immune active chronic HBV, comparing them with samples from healthy controls. In addition, gene expression profiles of B cells in the liver were analyzed by bulk and single-cell RNA-seq. Our data show a distinctive B-cell activation gene signature in the blood of patients with immune active chronic HBV, characterized by a significant upregulation of immune-related genes. This peripheral activation profile was also observed in B cells from the liver by single-cell RNA-seq, with naive and memory B-cell subsets being the primary carriers of the signature. Our findings suggest that B-cell gene profiles reflect responsiveness to HBV infection; these findings are relevant for clinical studies evaluating immunomodulatory treatment strategies for HBV.
ISSN:1537-6613
0022-1899
1537-6613
DOI:10.1093/infdis/jiae280