Identification of an autoantibody against alpha-enolase in primary biliary cirrhosis.
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.
Akisawa
N
N
The First Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
Maeda
T
T
Iwasaki
S
S
Onishi
S
S
D000208:Acute Disease; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006505:Hepatitis / Q000276:immunology; D006525:Hepatitis, Viral, Human / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000276:immunology*; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology; D011817:Rabbits; D012016:Reference Values
D001323:Autoantibodies; D007527:Isoenzymes; D011768:Pyruvate Dehydrogenase Complex; D010751:Phosphopyruvate Hydratase