Abstract
BackgroundStudies have shown that autoimmune response contributes to chronic hepatitis B (CHB) development.AimThis study aimed to identify autoantibodies in the sera of patients with CHB and to investigate the association of autoimmune response with disease severity in CHB.MethodsProteins from human liver carcinoma cell line HepG2 were separated by two-dimensional electrophoresis. The candidate autoantigens were recognized by serum autoantibodies from Chinese CHB patients. Immunohistochemical staining was performed to determine the hepatic expression of the autoantigen in CHB patients with different inflammatory grades. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the prevalence and the levels of serum autoantibody in CHB patients with different disease severity. Flow cytometry analysis was carried out to assess the autoreactive T cell response in the peripheral circulation of CHB patients.ResultsErbB-3-binding protein-1 (EBP-1) was identified as an autoantigen of serum autoantibodies in CBP patients. EBP-1 protein expression was upregulated in the liver of CHB patients with high-grade hepatic inflammation. The prevalence and levels of serum anti-EBP1 IgG were significantly increased in CHB patients with severe diseases compared with those with mild or moderate diseases, but none was detectable in the healthy controls. EBP-1 peptides induced proinflammatory cytokine expression in CD4+ T cells from CHB patients.ConclusionOur results demonstrate the presence of an autoantibody against EBP-1 in the sera as well as EBP-1-reactive T cells in the peripheral blood of CHB patient. EBP-1-induced autoimmune response is positively associated with the disease severity, suggesting that EBP-1-induced autoimmune response possibly contributes to progressive liver failure.
Highlights
Hepatitis B virus (HBV) infection is a major global public health problem that affects more than 240 million individuals worldwide, leading to chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma [1, 2]
We hypothesized that autoantigen/autoantibody-induced autoimmune response may contribute to liver inflammation in CHB and that the bystander T cells might represent a population of liver antigen-autoreactive T cells in CHB
To identify the liver proteins recognized by serum autoantibodies from Chinese CHB patients, proteins from HepG-2 cells were separated by 2-DE (Figure 1A), transferred to a polyvinylidene difluoride (PVDF) membrane, and incubated with a mixture of serum samples from CHB patients or healthy controls (HCs)
Summary
Hepatitis B virus (HBV) infection is a major global public health problem that affects more than 240 million individuals worldwide, leading to chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma [1, 2]. The liver histological features of CHB, such as portal and periportal lymphocyte infiltration and piecemeal necrosis of periportal hepatocytes [6], are very similar to those of autoimmune hepatitis (AIH) mediated by liver-targeting autoantibodies and autoreactive T cells [7]. Liver antigen-specific autoantibodies have been shown to contribute to periportal liver damage in CHB [8]. Studies on mouse hepatitis models have shown that the recruitment of non-HBV-specific bystander T cells contribute to the liver damage in CHB through creating a proinflammatory microenvironment [13,14,15,16]. We hypothesized that autoantigen/autoantibody-induced autoimmune response may contribute to liver inflammation in CHB and that the bystander T cells might represent a population of liver antigen-autoreactive T cells in CHB. Studies have shown that autoimmune response contributes to chronic hepatitis B (CHB) development
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