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FRI-136
Hepatitis B core antibody (anti-HBc) mirrors activation of
hepatitis B virus-specific immune responses and exhibits direct
effect on hepatitis B virus control
Chengcong Chen1, Yongyin Li1, Ling Guo1, Yang Zhou1, Xuan Yi1,
Xiaoyi Li1, Weibin Wang1, Xieer Liang1, Rong Fan1, Libo Tang1,
Jian Sun1, Jinlin Hou1. 1state key laboratory of organ failure research,
guangdong provincial key laboratory of viral hepatitis research,
department of infectious diseases, nanfang hospital, southern medical
university, Guangzhou, China
Email: [email protected]
Background and aims: Our previous work has shown that
quantitative levels of hepatitis B core antibody (qAnti-HBc) at
baseline is a useful predictor of antiviral therapy efficacy in HBeAgpositive
CHB patients (GUT, 2016). However there is little known
whether Anti-HBc is only a biomarker or it also plays a role in
controlling HBV, therefore, we aim to investigate the role of Anti-HBc
in chronic HBV infection.
Methods: Mouse model with hepatitis B virus (HBV) was established
by tail vein injection of pAAV8-HBV1.3 plasmid. After one month, the
stable HBV carrier mice were intraperitoneally injected with
acetaminophen (APAP). The serum levels of qAnti-HBc, ALT and
hepatitis B core-related antigen (HBcrAg), and the frequency and
function of intrahepatic CD8+ T cells from mice were detected.
Moreover, serum qAnti-HBc, the phenotype and function of lymphocytes
in peripheral blood and HBcAg expression in the liver tissue
from patients with chronic HBV infection were analysed by ELISA,
flowcytometry and Immunohistochemistry respectively. In addition,
in vitro assays were performed to examine the ability of Anti-HBc in
suppressing HBV replication.
Results: The levels of ALT and HBcrAg were significantly elevated at
day 1 after APAP injection in the HBV mouse model, and the levels of
qAnti-HBc were sequentially elevated. A significant correlation was
found between the serum qAnti-HBc levels and the frequency of
intrahepatic effector CD8+ T cells (CD44-CD62L-), and there was also
a positive correlation between serum qAnti-HBc levels and the
frequencies of intrahepatic IFN-gamma+CD8+ Tcells and IL-21+CD8+
T cells in the mouse model. Moreover, in patients with chronic HBV
infection, serum levels of qAnti-HBc were correlated with the
intrahepatic levels of HBcAg, the frequencies of periphery effector
CD8+T cells (CCR7-CD45RO-), and HBcAg-specific CD8+ T cells
respectively. An in vitro assay revealed that high levels of Anti-HBc
were able to directly suppress HBV replication in HepG2.2.15 cells.
Furthermore, Anti-HBc mediated the activation of complement to
lyse HepG2.2.15 cells and resulted in significantly reduced the levels
of HBsAg and HBeAg in the culture supernatant.
Conclusion: The generation of Anti-HBc mainly results from the
release of HBcAg from HBV-infected hepatocytes, and this marker
mirrors the activation of CD8+ T cell responses against HBV. The
notable demonstration of the direct antiviral effect of Anti-HBc
suggests that this antibody may have a potential value in the
treatment of chronic HBV infection. |
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发表于 2019-4-8 14:55