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P0474
CHARACTERISATION OF THE IMMUNE PROFILES OF CHRONIC
HEPATITIS B PATIENTS FOLLOWING NUC DISCONTINUATION
BY CyTOF MASS CYTOMETRY
L. Rivino1, M. Van Den Berg1, N. Le Bert2, S. Koh2, U.S. Gill3,
N.K. Hansi3, G.R. Foster3, A. Bertoletti1,2, P.T. Kennedy3. 1Emerging
Infectious Diseases, Duke-NUS Graduate Medical School, 2Infection &
Immunity Program, Singapore Institute for Clinical Sciences, Agency
for Science, Technology & Research (A*STAR), Singapore, Singapore;
3Hepatology Unit, Centre for Digestive Diseases, Blizard Institute,
Barts and The London SMD, QMUL, London, United Kingdom
E-mail: [email protected]
Background and Aims: It is currently not possible to predict
whether the discontinuation of nucleos(t)ide analogues (NUCs) in
Chronic Hepatitis B virus (HBV) patients will be followed by viral
relapse and hepatic flares (HF). Through the utilisation of cytometry
time of flight (CyTOF), a novel mass cytometry technology, in
conjunction with traditional flow cytometry tools, we aim to
establish an immune profile associated with the onset of HF upon
therapy discontinuation.
Methods: Cytokine and chemokine serum levels (IL-1b, IL-6,
TNF-a, IL-10, CXCL-8, CXCL-10) were measured longitudinally using
Luminex in chronic HBV patients who developed HF (n = 6) and
those who did not (n = 2) upon discontinuation of NUCs. HBVspecific
T cell responses were assessed after in vitro expansion of
patient peripheral blood mononuclear cells with overlapping HBV
peptides pools. An in-depth longitudinal analysis of the expression
of 35 markers involved in the activation, differentiation, exhaustion
and anti-viral effector function of T and NK cells is performed by
CyTOF mass cytometry.
Results: The rise in serum ALT following viral relapse after therapy
discontinuation are associated with a significant increase in the
serum levels of CXCL-10 and IL-10. Despite comprehensive analysis
of HBV-specific T cells using HBV peptides, functional antigenspecific
T cells in the periphery were not detected. Preliminary
analysis by CyTOF reveals significant differences in the frequency
and functionality of T and NK cell populations longitudinally
(during and after discontinuation of therapy), between patients
characterised by viral relapse and those with immune control.
Conclusions: Consistent with previous studies, HF are associated
with increased serum levels of CXCL-10 and IL-10 while HBVspecific
T cells remain undetectable in the periphery. The absence
of circulating virus-specific CD8+T cells during HF suggests that
hepatic inflammation following NUC withdrawal in chronic HBV
patients is induced independent of virus-specific CD8+ T cells.
CyTOF technology allows us to investigate an unprecedented
number of parameters (currently up to 42) for a more detailed
assessment of biomarkers associated with sustained immune
control of HBV.
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发表于 2015-4-20 16:53