The characterization of immune response in patients with viral hapatitis B infection

Abstract

Hepatitis B infection is a major cause of liver diseases. Approximately 2 billion people worldwide and 400 million of them remain chronically infected. Defect or exhausted innate and adaptive immune responses lead to HBV persistence. It is believed that the vigorous and multispecific T-cell response are important to viral control in resolved HBV infection. Here, we firstly identified novel HLA-C-restricted CTL epitope of HBV antigen from resolved patient. The specific CTL response to amino acids 171-180 of envelope antigen restricted to HLA-Cw*08:01 molecule revealed responsiveness in 53% of tested patients with resolved HBV infection. The cross-activity of this CTL response was detected in HBV genotype B and C. The comparative specific CTL response against Env171-180 versus the known-HLA-A or -B-restricted epitopes indicated that the frequency and magnitude of HLA-Cw*08:01-restricted Env171-180 response are greater or at least comparable to known HLA-A*02, A*11, A*24 and B*51 restricted CTL responses. Moreover, we investigated whether gene expression patterns in peripheral blood mononuclear cells (PBMC) were different between sustained virological responder and non-responder to Pegylated-interferon alpha in chronic HBV infection with positive or negative HBeAg. The Illumina Sentrix Humanref-8 v2 BeadChips microarray was used for the analysis of global gene expression. We found that most of the significantly different genes were at higher level in the responder compared to the non-responder groups both at pretreatment and/or during treatment at week 24. Some interesting immune-related genes are previously reported to have anti-viral activity such as response to virus (IFI16, MX1, MX2), viral defense or viral genome sensor (GBP3, IFI16), regulation of viral reproduction (APOBEC3F) and proteasome (PSMB8). Another factor which influences the chronic status of HBV infection is host factor. Several polymorphisms of immune genes, such as cytokine genes, were previously reported to be individually associated with disease progression; however, the analysis of these polymorphisms together as the combination of Th1 and Th2 genotypes has never been investigated. In this study, twenty-two polymorphisms of cytokine and cytokine receptor genes were studied for their association with the risk of chronicity. Although the combined analysis of the role of Th1 and Th2 genotypes gave no positive association with chronic hepatitis B infection. Our genotype data showed that the patients with low IL-10 as well as low IL-4 producing allele has lower risk for chronic state suggesting a protective role of Th2. Taken together, host factors affect the distinct immune responses resulting in the different clinical outcomes of HBV infection. The more information in HBV pathogenesis and immune response is necessary for the further development of novel therapy for chronic HBV infection.