| Zdroj: |
Le Bert, N, Gill, U S, Hong, M, Kunasegaran, K, Tan, D Z M, Ahmad, R, Cheng, Y, Dutertre, C-A, Heinecke, A, Rivino, L, Tan, A, Hansi, N K, Zhang, M, Xi, S, Chong, Y, Pflanz, S, Newell, E W, Kennedy, P T F & Bertoletti, A 2020, ' Effects of Hepatitis B Surface Antigen on Virus-specific and Global T Cells in Patients With Chronic HBV infection ', Gastroenterology, vol. 159, no. 2, pp. 652-664 . https://doi.org/10.1053/j.gastro.2020.04.019 |
| Popis: |
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; PCONCLUSIONS: 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. |
