Effects of Hepatitis B Surface Antigen on Virus-specific and Global T Cells in Patients With Chronic HBV infection

Abstract

Background & aims: Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen, HBsAg) and the duration of infection-most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients' lymphocyte and HBV-specific T-cell populations. Methods: We collected blood samples and clinical data from 243 patients with HBV infection (3-75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, HBeAg, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMC). In PBMC from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer (NK) and T cells by mass cytometry. PBMC from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma ELISpot assays or flow cytometry. We used multivariate linear regression and performed variable selection using Akaike's information criterion to identify covariates associated with HBV-specific responses of T cells. Results: Although T and NK cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg (r=0.3367; P<.00001). After we performed the variable selection, the multivariate linear regression model identified patient age as the only factor significantly associated with numbers of HBs-specific T cells (P=.000115). In patients younger than 30 years, HBs-specific T cells constituted 28.26% of the total HBV-specific T cells; this value decrease to 7.14% in patients older than 30 years. Conclusions: In an analysis of immune cells from patients with chronic HBV infection, we found the duration of HBsAg exposure, rather than quantity of HBsAg, associates with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should consider patients younger than 30 years.