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Immunologische Phänomene bei Leberkrankheiten: Die Bedeutung mitochondrialer Antikörper

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Zusammenfassung

Antikörper gegen Zellkerne, glatte Muskulatur und Mitochondrien lassen sich bei der primären biliären Lebercirrhose, der chronisch aktiven Hepatitis und Fällen von kryptogener Lebercirrhose nachweisen.

Mitochondriale Antikörper kommen bei der biliären Cirrhose in etwa 90% der Fälle vor, bei den beiden anderen Krankheiten in etwa 24–26%.

Die pathogenetische Rolle dieser organunspezifischen und heterologen Antikörper ist nicht geklärt. Ihr Nachweis hat differentialdiagnostische Bedeutung, da Seren von Patienten mit extrahepatischem Ikterus, sekundärer Lebercirrhose oder einer akuten Virus-Hepatitis nicht oder nur niedertitrig mit diesen Antigenen in der Immunofluorescenz reagieren.

Die bei der primären biliären Lebercirrhose vorkommenden mitochondrialen Autoantikörper sind mit einem Antigen innerer mitochondrialer Membranen assoziiert. Leicht extrahierbare Membranproteine und die Enzyme der Elektronentransportkette sind an der immunologischen Reaktion nicht beteiligt. Das membrangebundene Antigen ist ein Lipoprotein und könnte mit Transportproteinen, die auch von Bakterien-Membranen bekannt sind, im Zusammenhang gebracht werden. Die Entstehung dieser Antikörper als Folge einer Kreuzreaktion mit Membranenzymen bestimmter Mikroorganismen ist deshalb nicht auszuschließen.

Summary

Tissue antibodies against nuclei, smooth muscles and mitochondria are very largely confined to three recognised liver diseases: primary biliary cirrhosis (PBC), activ chronic hepatitis and cryptogenic cirrhosis.

Mitochondrial antibodies occur in about 90% of patients with PBC and in 24–26% of patients with the two other liver diseases.

Their role in the pathogenesis of these disorders is still undefined, but it is of diagnostic importance that these tissue antibodies are not found in cirrhosis due to known insults — e.g., alcoholism, Wilson's disease and haemochrommatosis—or in the different forms of secondary biliary cirrhosis, related to main duct obstruction, congenital atresia or sclerosing cholangitis.

The autoantibodies found in sera of patients with primary biliary cirrhosis have been shown to react with a component of the mitochondrial inner membranes. The enzymes of the electron transport chain and a number of readily extractable mitochondrial proteins were not associated with the membrane fragment containing the antigen. There is some evidence that the antigen, which is a lipoprotein, may be a membrane-transport-protein.

Since inner membranes have structural similarities with the coat of some viruses or bacteria the formation of mitochondrial antibodies due to cross reaction with as yet unidentified microorganisms cannot be excluded.

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Authors and Affiliations

  1. Medizinische Universitätsklinik Tübingen, Germany

    P. A. Berg, D. Doniach & I. M. Roitt

  2. Department of Immunology, Middlesex Hospital, W1, London

    P. A. Berg, D. Doniach & I. M. Roitt

Authors
  1. P. A. Berg
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  2. D. Doniach
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  3. I. M. Roitt
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Additional information

Herrn Prof. Dr. Dr. h. c. H. E. Bock zum 65. Geburtstag.

Die im Department of Immunology (Middlesex Hospital, London) durchgeführten Untersuchungen wurden unterstützt von dem Medical Research Council (Great Britain), dem Arthritis and Rheumatism Council, der Nuffield Foundation, der World-Health Organization, der Volkswagenwerk-Stiftung und der Dr. Karl Merck-Stiftung.

Miss Heather Cooper sei an dieser Stelle für die ausgezeichnete technische Hilfe bei der Ausführung des experimentellen Teils dieser Arbeit besonders gedankt.

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Berg, P.A., Doniach, D. & Roitt, I.M. Immunologische Phänomene bei Leberkrankheiten: Die Bedeutung mitochondrialer Antikörper. Klin Wochenschr 47, 1297–1307 (1969). https://doi.org/10.1007/BF01484292

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