Antimitochondrial antibodies in primary biliary cirrhosis recognize both specific peptides and shared epitopes of the M2 family of antigens

Authors

  • Graham R. Flannery,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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    • Department of Genetics and Human Variation, La Trobe University, Bundoora, Victoria 3083, Australia.

  • Andrew K. Burroughs,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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  • Patrice Butler,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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  • Jeyananthan Chelliah,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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  • Jeremy Hamilton-Miller,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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  • William Brumfitt,

    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
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  • Professor Harold Baum

    Corresponding author
    1. Biochemistry Department, King's College London, London W8 7AH, and Academic Department of Medicine Department of Medical Microbiology, Royal Free Hospital and School of Medicine, London NW3, 2PF, United Kingdom
    • Department of Biochemistry, King's College London, Campden Hill Road, London W8 7AH, United Kingdom
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Abstract

Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common “M2 epitope” that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.

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