Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients.

ABSTRACT: Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, and increase functional cure rates. However, little is known about pre-treatment HBsAg levels as an indicator of HBV immune potential. Here, we compared the phenotypes and HBV-specific response of lymphocytes in CHB patients stratified by serum HBsAg levels <500 (HBs^lo) or >50,000?IU/ml (HBs^hi) using immunological assays (flow cytometry, ICS, ELISPOT). HBs^hi patients had significantly higher expression of inhibitory PD-1 on CD4⁺ T cells, particularly among TEMRA subset, and higher FcRL5 expression on B cells. Upon HBcAg(core) or HBsAg(env)-stimulation, 85% and 60% of HBs^lo patients had IFN?⁺TNF?⁺ and IFN?⁺ IL2⁺ CD4⁺ T cell responses respectively, in comparison to 33% and 13% of HBs^hi patients. Checkpoint blockade with ?PD-1 improved HBV-specific CD4⁺ T cell function only in HBs^lo patients. HBsAg-specific antibody-secreting cells (ASCs) response was not different between these groups, yet ?PD-1 treatment resulted in significantly higher fold change in ASCs among patients with HBsAg <100?IU/ml compared to patients with HBsAg >5,000?IU/ml. Thus, serum HBsAg correlates with inhibitory receptor expression, HBV-specific CD4⁺ T cell responses, and augmentation by checkpoint blockade.

SUBMITTER: Kim JH 

PROVIDER: S-EPMC7000714 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature