Autoantibodies in primary biliary cirrhosis: Analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes

✍ Scribed by Shelley P. M. Fussey; J. Gordon Lindsay; Christopher Fuller; Richard N. Perham; Susan Dale; Oliver F. W. James; Margaret F. Bassendine; Stephen J. Yeaman

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 881 KB
• Volume: 13
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840130314

✦ Synopsis

S i x components of the mammalian 2-0x0 acid dehydrogenase complexes have previously been identified as M2 autoantigens in primary biliary cirrhosis. In this report, we present data showing that both polypeptidespecific and cross-reacting antibodies are present in patients' sera. Antibodies reacting with E2 of the pyruvate dehydrogenase complex cross-react with protein X but not with any other mammalian antigen. The main immunogenic region on protein X has been localized to within its single lipoyl domain. Polypeptide-specific antibodies bind to E l a and E l @ of the pyruvate dehydrogenase complex. Antibodies reacting with the E2 polypeptides of the 2-oxoglutarate dehydrogenase complex and branched-chain 2-0x0 acid dehydrogenase complex show some crossreactivity but do not recognize any of the antigens of the pyruvate dehydrogenase complex. Antibodies against the E2 component of the mammalian pyruvate dehydrogenase complex cross-react effectively with the corresponding protein from yeast but not with E2 from Escherichia coli. Antibody titer against mammalian antigens is significantly higher than against the bacterial antigens, arguing against a bacterial origin for primary biliary cirrhosis. (HEPATOLOGY 1991;13:467-

474.)

PBC is a chronic autoimmune liver disease in which the initial focal destruction of the intrahepatic bile ducts is followed ultimately by the development of cirrhosis and liver failure (1). PBC is characterized by the presence of nonspecies-specific antimitochondrial antibodies (AMA) in the sera, which are directed against a