Tracking B cell immunity during perturbation of hepatitis B infection induced by treatment withdrawal

作者：Sabela Lens, Alice R. Burton, Jessica Davies, Maëlle Locatelli, Mireia García‐López, Anna Pocurull, Anna Jeffery-Smith, Nikolai Novikov, Simon P. Fletcher, Xavier Forns, Sofía Pérez‐del‐Pulgar, Mala K. Maini · 发表于：Gut · 年份：2025 · DOI：10.1136/gutjnl-2024-333309 · 被引用次数：5 · 研究领域：Hepatitis B Virus Studies、Organ Transplantation Techniques and Outcomes、T-cell and B-cell Immunology

BACKGROUND: Withdrawal of prolonged nucleos(t)ide analogue (NA) treatment results in hepatitis B surface antigen (HBsAg) loss in some subjects with chronic hepatitis B (CHB), potentially revealing immune correlates of functional cure. OBJECTIVE: We investigated whether baseline or longitudinal changes in humoral immunity correlated with outcome of discontinuing prolonged NA treatment. DESIGN: Global memory B cells (MBC) and T follicular helper cells (Tfh) were analysed by flow cytometry. HBs (small surface)/HBc (core)-MBC were quantified by ex-vivo bait staining and function assessed by cultured ELISpots (enzyme-linked immunosorbent spots). Immune parameters assessed at end-of-treatment (EOT), 12 and 48 weeks after treatment withdrawal (and at 4-8 years in a subset) were correlated with intrahepatic and longitudinal serum viral markers and alanine transaminase (ALT). RESULTS: and functionally defective. Following treatment withdrawal, increases in class-switched HBc-MBC were frequently temporally linked with hepatic flares. Subjects achieving HBsAg loss had an increase in activated global MBC detectable at EOT that become more marked by week 48, accompanied by significant increases in plasmablasts. HBs-MBC in those with HBsAg loss showed significant reductions in PD-1, trends to increased activation (CD71) and function and a more robust correlation with Tfh, compared with HBsAg persistence. MBC changes were maintained 4-8 years after HBsAg seroconversion. CONCLUSION: Differen...