Mitochondrial antibodies in primary biliary cirrhosis: Species and nonspecies specific determinants of M2 antigen

Authors

  • Jutta Lindenborn-Fotinos,

    1. Department of Medicine, University of Tübingen, Tübingen, Federal Republic of Germany and Department of Biochemistry, Chelsea College, University of London, London, England
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  • Harold Baum,

    1. Department of Medicine, University of Tübingen, Tübingen, Federal Republic of Germany and Department of Biochemistry, Chelsea College, University of London, London, England
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  • Professor Peter A. Berg M.D.

    Corresponding author
    1. Department of Medicine, University of Tübingen, Tübingen, Federal Republic of Germany and Department of Biochemistry, Chelsea College, University of London, London, England
    • Medizinische Klinik, University of Tübingen, Otfried-Müller-Str., D-74 Tübingen, Federal Republic of Germany
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Abstract

Sera from patients with primary biliary cirrhosis reacted with four major bands in beef heart mitochondria and ATPase extract when analyzed by immunoblot after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These four immunologically reactive bands corresponded to protein bands with molecular weights of about (a) 80,000; (b) 63,000; (c) 56,000; and (d) 43,000 to 46,000. An additional immunoreactive band was found with some high-titered primary biliary cirrhosis sera at 36,000. No association with any ATPase subunits was found, except for band c which migrated between the α- and β-subunit of ATPase. Most ATPase fractions did not contain this band c, indicating that M2 determinants, as defined by immunoblot, are not identical with any ATPase subunit.

Species and nonspecies-specific determinants of M2 were identified using mitochondria from rat liver and human heart and liver. Antigenic bands a, c and d were nonspecies-specific. Band b and e occurred only in beef heart. An additional determinant at about 38,000 was detected using human heart and liver mitochondria. Primary biliary cirrhosis sera showed a typical reaction with two protein bands of Escherichia coli, one at about 85,000 to 90,000 and the other at 60,000. Antibodies against both determinants could be absorbed with submitochondrial particles of beef heart showing that E. coli shares cross-reacting determinants with mitochondria.

Sera from 56 primary biliary cirrhosis patients were tested using beef heart mitochondria. Fifty-four sera reacted positively with the M2 antigen in the ELISA, and these sera reacted with at least 1 of the 4 major antigenic bands: 85% were positive with band a and/or band b; 15% detected exclusively band c and none of the latter fixed complement. Antimitochondrial antibodypositive sera possessing other specificities (anti−M1, −M3, −M5, −M6 and −M7) were negative. A correlation with the precipitating antimitochondrial antibody system was not found.

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