BACKGROUND: Primary biliary cirrhosis is a chronic cholestatic liver disease in which autoreactive T cells may play an important role in the destruction of intrahepatic bile ducts. However, target antigens remain unknown. Alpha-enolase-derived peptide binds to human leukocyte antigen (HLA)-DR8, which is implicated in the development of primary biliary cirrhosis in Japanese patients. Partial homology between alpha-enolase and the inner lipoyl domain of E2 component of pyruvate dehydrogenase (PDH-E2) is also observed. METHODS: Using alpha, beta and gamma enolase isozymes obtained from humans and/or rabbits, we examined serum samples of 56 patients with primary biliary cirrhosis, 19 autoimmune hepatitis, 38 acute and chronic viral hepatitis and 36 healthy subjects by immunoblotting. RESULTS: Anti-alpha-enolase antibody was present in a significantly higher percentage of patients with primary biliary cirrhosis (16 of 56, 28.6%) and autoimmune hepatitis (6 of 19, 31.6%) than in normal subjects (p<0.005, p<0.01, respectively). Antibodies against beta and gamma-enolases were not detected in any serum sample. Although there was no significant correlation between the presence of anti-alpha-enolase antibody and clinical features of primary biliary cirrhosis, the mortality rate associated with hepatic failure in patients with positive autoantibody was significantly higher than that of antibody-negative PBC patients (6 of 16, 37.5% vs 5 of 40, 12.5%, p<0.05). CONCLUSIONS: Since alpha-enolase is expressed on the cell surface, our data suggest that the immunological reaction to alpha-enolase might be involved in biliary epithelial destruction and be relevant to the disease progression.
BACKGROUND:Primary biliary cirrhosis is a chronic cholestatic liver disease in which autoreactive T cells may play an important role in the destruction of intrahepatic bile ducts. However, target antigens remain unknown. Alpha-enolase-derived peptide binds to human leukocyte antigen (HLA)-DR8, which is implicated in the development of primary biliary cirrhosis in Japanese patients. Partial homology between alpha-enolase and the inner lipoyl domain of E2 component of pyruvate dehydrogenase (PDH-E2) is also observed. METHODS: Using alpha, beta and gamma enolase isozymes obtained from humans and/or rabbits, we examined serum samples of 56 patients with primary biliary cirrhosis, 19 autoimmune hepatitis, 38 acute and chronic viral hepatitis and 36 healthy subjects by immunoblotting. RESULTS: Anti-alpha-enolase antibody was present in a significantly higher percentage of patients with primary biliary cirrhosis (16 of 56, 28.6%) and autoimmune hepatitis (6 of 19, 31.6%) than in normal subjects (p<0.005, p<0.01, respectively). Antibodies against beta and gamma-enolases were not detected in any serum sample. Although there was no significant correlation between the presence of anti-alpha-enolase antibody and clinical features of primary biliary cirrhosis, the mortality rate associated with hepatic failure in patients with positive autoantibody was significantly higher than that of antibody-negative PBC patients (6 of 16, 37.5% vs 5 of 40, 12.5%, p<0.05). CONCLUSIONS: Since alpha-enolase is expressed on the cell surface, our data suggest that the immunological reaction to alpha-enolase might be involved in biliary epithelial destruction and be relevant to the disease progression.
Authors: Dénison S Sánchez-Miguel; Jahir Romero-Jiménez; César A Reyes-López; Ana Lilia Cabrera-Avila; Normande Carrillo-Ibarra; Claudia G Benítez-Cardoza Journal: Protein J Date: 2010-01 Impact factor: 2.371
Authors: Brandy R Lu; Stephen M Brindley; Rebecca M Tucker; Cherie L Lambert; Cara L Mack Journal: Gastroenterology Date: 2010-07-23 Impact factor: 22.682