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

Authors

  • Shelley P. M. Fussey,

    1. Departments of Biochemistry and Geneticsa, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
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  • J. Gordon Lindsay,

    1. Department of Biochemistry, University of Glasgow, Glasgow G12 8QQ, United Kingdom
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  • Christopher Fuller,

    1. Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
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  • Richard N. Perham,

    1. Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom
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  • Susan Dale,

    1. Departments of Biochemistry and Geneticsa, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
    Current affiliation:
    1. Department of Biochemistry, University of Dundee, Dundee DD1 4HN, United Kingdom
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  • Oliver F. W. James,

    1. Department of Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
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  • Margaret F. Bassendine,

    1. Department of Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
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  • Stephen J. Yeaman Ph.D.

    Corresponding author
    1. Departments of Biochemistry and Geneticsa, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom
    • Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK
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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 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 Elα and E1β 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 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.)

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