FRI-131
Impact of HBsAg level on cellular immune responses in HBeAg
negative patients with chronic hepatitis B virus infection
Elmira Aliabadi1,2, Carola Mix1,2, Michael P. Manns1,2,3, Anke Kraft1,2,
Markus Cornberg1,2,3. 1Hannover Medical School, Department of
Gastroenterology, Hepatology and Endocrinology, 30625, Hannover,
Germany; 2German Centre for Infection Research (Deutsches Zentrum
für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig,
30625, Hannover, Germany; 3Centre for Individualized Infection
Medicine (CIIM), c/o CRC Hannover, 30625, Hannover, Germany
Email: [email protected]
Background and aims: Worldwide 250 million people are persistently
infected with hepatitis B virus (HBV) leading to 686.000 deaths
annually. The level of hepatitis B surface antigen (HBsAg) produced
by HBV-infected hepatocytes could have an immunomodulatory role
in HBV infected patients. However, the correlation between HBsAg
level and HBV-specific T cell immune responses in patients with
chronic HBV (CHB) and HBeAg negative has not been well defined.We
investigated HBV-specific immune responses in HBeAg negative
patients with different levels of HBsAg during the natural course of
chronic hepatitis B.
Method: 44 HBeAg negative patients were categorized into 4 groups
based on their HBsAg level (HBsAg < 100 IU/ml, HBsAg 100–999 IU/
ml, HBsAg 1, 000-9, 999 IU/ml, HBsAg ≥ 10, 000 IU/ml). PBMCs were
isolated from these patients and different subsets of immune cells
were phenotypically characterized using 14 color flow cytometry.
Furthermore, IFNγ+ HBV-specific T cell responses were measured
after in vitro culture with overlapping peptides covering polymerase,
surface and core of HBV genotype D in the presence or absence of
anti-PD-L1 antibody.
Results: Patients with different levels of HBsAg showed similar
frequencies of memory, naïve and effector T cells, γδ T cells, Treg cells,
MAIT cells, B cells, NK cells, monocytes and DCs. Interestingly, the
frequency of γδ T cells, Treg cells and CD1c- myeloid DCs was
significantly increased in CHB patients compared to healthy
individuals.
Stimulation of PBMCs with HBV overlapping peptides induced core and
polymerase-specific T cell responses. However, surface-specific T
cell responses were hardly detectable. We observed a trend towards
higher HBV-specific T cells in patients with HBsAg < 100 IU/ml. In
patients with HBsAg ≥ 10, 000 IU/ml a high variability of T cell
responses were detected. Interestingly, in these patients stronger Tcell responses were associated with young age, female gender and
low HBV DNA. In general, CD4+ T cell response to in vitro stimulation
with HBV overlapping peptides was stronger than CD8+ T cell
responses. Blocking the PD-1/PD-L1 pathway during in vitro culture
significantly increased the core-specific T cell response in patients
with HBsAg < 100 IU/ml.
Conclusion: Our data suggests that HBsAg level per se may have only
a minor impact on the cellular immune responses. Patients with
HBsAg < 100 IU/ml, showed slightly stronger T cell responses to in
vitro HBV peptide stimulation especially after using checkpoint
inhibitors. Therefore, patients with low HBsAg levels may demonstrate
better responses to immune-modulatory treatment.作者: StephenW 时间: 2019-4-8 14:50