Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: Identification and characterization by radioimmunoassay and immunoblotting

Authors

  • Professor Dr. Michael Manns,

    Corresponding author
    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
    • Medizinische Klinik und Poliklinik, University of Mainz, Langenbeckstr. 1, D-6500 Mainz 1, Federal Republic of Germany
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  • Guido Gerken,

    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
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  • Apostolos Kyriatsoulis,

    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
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  • Christian Trautwein,

    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
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  • Konrad Reske,

    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
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  • Karl-Hermann Meyer Zum Büschenfelde

    1. I. Medizinische Klinik und Poliklinik and Institut für Immunologie, Johannes Gutenberg-Universität Mainz, D-6500 Mainz, Federal Republic of Germany
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  • This paper is dedicated to the 70th birthday of Professor Dr. Paul Schölmerich.

Abstract

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radio-immunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti-p 62 and anti-p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug-induced pseudo-lupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluo-rescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin- and chymotrypsin-sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm3 and p 48 at 1.30 gm per cm3. Thus, radio-immunoassays have been developed that specifically detect two distinct primary biliary cirrhosis-specific subtypes of antimitochondrial antibodies: anti-p 62 and anti-p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes. The reaction of antimitochondrial antibodies with mitochondrial antigens p 62 and p 48 is due to different autoantibody subtypes and not due to identical determinants on different polypeptides.

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