Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes.
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.
Fussey
S P
SP
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, United Kingdom.
Lindsay
J G
JG
Fuller
C
C
Perham
R N
RN
Dale
S
S
James
O F
OF
Bassendine
M F
MF
Yeaman
S J
SJ
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
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)