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J Virol. 2011 Mar;85(5):2416-28. Epub 2010 Dec 8.
Immune and viral profile from tolerance to hepatitis B surface antigen
clearance: a longitudinal study of vertically hepatitis B virus-infected
children on combined therapy.
Carey I, D'Antiga L, Bansal S, Longhi MS, Ma Y, Mesa IR, Mieli-Vergani G,
Vergani D. Institute of Liver Studies, King's College Hospital, London SE5
9RS, UK.
Abstract
The aim of the study was to investigate longitudinally hepatitis B virus
(HBV)-specific T-cell reactivity and viral behavior versus treatment
response in tolerant children during combined antiviral therapy.
Twenty-three children with infancy-acquired hepatitis B (HBeAg(+))
belonging to a published pilot study of 1-year treatment with
lamivudine/alpha interferon (IFN-α) were investigated. Five seroconverted
to anti-HBs (responders). Nine were HLA-A2(+) (4 responders and 5
nonresponders). Mutations within the HBV core gene were determined at
baseline in liver and in serial serum samples by direct sequencing at
baseline; during treatment week 2 (TW2), TW9, TW28, and TW52; and after
follow-up week 24 (FUW24) and FUW52. HBV-specific reactivity was evaluated
by T-cell proliferation with 16 HBV core 20-mer overlapping peptides and by
HLA-A2-restricted core(18-27) pentamer staining and CD8(+) IFN-γ
enzyme-linked immunospot (ELISPOT) assay. HBV core-specific T-cell
proliferative and CD8 responses were more vigorous and broader among
responders than among nonresponders at TW28 and TW52, while the number of
mutations within HBV core gene immunodominant epitopes was lower at TW28
and was negatively associated with HBV-specific T-cell proliferative
responses at both time points. The HBV DNA viral load was negatively
associated with HBV-specific T-cell proliferative and CD8 responses during
treatment, especially at TW28. Treatment-induced transition from
immunotolerance to HBV immune control is characterized by the emergence of
efficient virus-specific immune responses capable of restraining mutations
and preventing viral evasion.
PMID: 21147914 [PubMed - indexed for MEDLINE] |
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