title: Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes.
abstract: Six components of the mammalian 2-oxo acid dehydrogenase complexes have previously been identified as M2 autoantigens in primary biliary cirrhosis. In this report, we present data showing that both polypeptide-specific 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 E1 alpha and E1 beta of the pyruvate dehydrogenase complex. Antibodies reacting with the E2 polypeptides of the 2-oxoglutarate dehydrogenase complex and branched-chain 2-oxo acid dehydrogenase complex show some cross-reactivity 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.
authors.affiliation: Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: S P
authors.initials: SP
authors.lastname: Fussey
authors.forename: J G
authors.initials: JG
authors.lastname: Lindsay
authors.forename: C
authors.initials: C
authors.lastname: Fuller
authors.forename: R N
authors.initials: RN
authors.lastname: Perham
authors.forename: S
authors.initials: S
authors.lastname: Dale
authors.forename: O F
authors.initials: OF
authors.lastname: James
authors.forename: M F
authors.initials: MF
authors.lastname: Bassendine
authors.forename: S J
authors.initials: SJ
authors.lastname: Yeaman
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D001323:Autoantibodies / Q000276:immunology*; D003429:Cross Reactions; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007658:Ketone Oxidoreductases / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008928:Mitochondria / Q000276:immunology; D009097:Multienzyme Complexes / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011549:Pseudomonas / Q000276:immunology; D030481:Pyruvate Dehydrogenase (Lipoamide); D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology; D012440:Saccharomyces / Q000276:immunology
chemical_list: D001323:Autoantibodies; D009097:Multienzyme Complexes; C045867:PDHX protein, human; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D007658:Ketone Oxidoreductases; D030481:Pyruvate Dehydrogenase (Lipoamide); D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)