Abstract
BackgroundFunction exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand various diseases. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV) induced hepatitis, hindering the comprehensive understanding to this severe disease.AimTo identify the major proteins in the progression of HBV infection from mild stage to severe stage.MethodsWe performed an integrated strategy by combining two-dimensional electrophoresis (2-DE), peptide mass fingerprinting (PMF) analysis, and tissue microarray techniques to screen the functional proteins and detect the localization of those proteins.ResultsInterestingly, MS/MS identification revealed the expression level of alpha-1 antitrypsin (AAT) was significantly elevated in serum samples from patients with severe chronic hepatitis. Immunoblotting with a specific AAT antibody confirmed that AAT is highly expressed in serum samples from patients with hepatic carcinoma and severe chronic hepatitis. Furthermore, we observed that AAT is with highest expression in normal tissue and cells, but lowest in hepatic carcinoma and severe chronic hepatitis tissues and cells, suggesting the specific secretion of AAT from tissues and cells to serum.ConclusionThese results suggest the possibility of AAT as a potential biomarker for hepatitis B in diagnosis.
Highlights
Alpha-1 antitrypsin (AAT) is the most prominent protease inhibitor in human serum
These results suggest the possibility of alpha-1 antitrypsin (AAT) as a potential biomarker for hepatitis B in diagnosis
Patient Materials Approved by the local ethics committee, 31 chronic hepatitis B patients (13 mild and 18 severe), 10 convalescent acute hepatitis B (AHB), 18 hepatitis B virus (HBV)-related Hepatocellular Carcinoma (HCC) patients and 12 healthy blood donors were enrolled in this study
Summary
Alpha-1 antitrypsin (AAT) is the most prominent protease inhibitor in human serum. More than 70 genetic variants of AAT have been described. It was documented that ATT deficiency associates with various types of liver diseases, such as neonatal hepatitis [1], cirrhosis and hepatoma [2]. Chronic infection is associated with significant morbidity and mortality as a result of long-term sequelae including inflammatory liver disease, cirrhosis, and hepatocellular carcinoma [3]. It’s well known that different functions of specific proteins play crucial roles in hepatitis B virus (HBV) induced hepatitis, comprehensive identification of those specific proteins may. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV) induced hepatitis, hindering the comprehensive understanding to this severe disease
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