Virus-Specific Immune Response in HBeAg-Negative Chronic Hepatitis B: Relationship with Clinical Profile and HBsAg Serum Levels

Abstract

Background & AimsThe immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV.MethodsPeripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay.ResultsThe total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.ConclusionsDifferent clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.

Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection

“…In a previous study, we demonstrated that the direct interaction of HBsAg with human monocytes and macrophages interferes with the activation of intracellular signaling pathways regulating the production of IL-12 (12). Because the induction of HBV core-specific T cell responses is inversely correlated with the serum HBsAg concentration (13), we hypothesized that the high concentration of circulating HBsAg that is found during HBV infection may facilitate the development of MDSCs and may be responsible for the attenuation of HBVspecific T cell responses, leading to the persistence of HBV.…”

Hepatitis B Virus-Related Hepatocellular Carcinoma: Pathogenic Mechanisms and Novel Therapeutic Interventions

“…Robust anti-core T cell responses were found in patients with reduced HBsAg serum levels, suggesting that corespecific T cell responses mediated a protective effect in HBV control [77] . These results suggested that expansion of HBV-specific T cells in vitro through HBcAg stimulation may be one immunotherapeutic intervention.…”

Immune therapy for hepatitis B

“…Non-antigen-specific immune therapeutic approaches in patients with CHB Logic and ethical basis Decreased levels of cytokine, impaired functions of HBVspecific immunocytes, lower levels of natural killer cells, dysfunctional antigen-presenting DC and increased activities of immune suppressor cells have been shown by various researchers in patients with CHB (47)(48)(49)(50)(51). This provided an impression that the decreased immune responses of CHB patients may contribute to viral persistence and liver damages.…”