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Detection of novel non-M2-related antimitochondrial antibodies in patients with anti-M2 negative primary biliary cirrhosis
  1. Manon Feuchtinger
  1. Department of Internal Medicine, University of Tuebingen, Germany
    1. Stine Christ
    1. Department of Internal Medicine, University of Tuebingen, Germany
      1. Beate Preuss (preuss.beate{at}web.de)
      1. Department of Internal Medicine, University of Tuebingen, Germany
        1. Jörn Dengjel
        1. Interfacultary Institute for Cellular Immunology, University of Tuebingen, Germany
          1. Susanne Duman
          1. Department of Internal Medicine, University of Tuebingen, Germany
            1. Stefan Stevanovic (stefan.stevanovic{at}uni-tuebingen.de)
            1. Interfacultary Institute for Cellular Immunology, University of Tuebingen, Germany
              1. Reinhild Klein (reinhild.klein{at}med.uni-tuebingen.de)
              1. Department of Internal Medicine, University of Tuebingen, Germany

                Abstract

                Objective: In 95% of patients with primary biliary cirrhosis (PBC) antimitochondrial antibodies (AMA) can be detected reacting with at least one of the five components of the M2-antigen identified as 2-oxo-acid-dehydrogenase complex (OADC). However, among our PBC-sera 15-20% are anti-M2 negative by ELISA and Western blotting (WB) but show in the immunofluorescence test (IFT) the typical AMA-staining. Aim of the present study was, to characterize the target antigen(s) of these non-M2-related AMA.

                Patients and methods: Analyzed were sera from 27 patients with clinically and histologically proven PBC being AMA positive by IFT but anti-M2 negative by ELISA and WB. They were tested by WB against various 100.000 g supernatants obtained after sonication of mitochondria from rat liver, bovine heart and pig kidney. These were further separated by isopycnic sucrose density centrifugation using different sucrose density fractions.

                Results: Fourteen of the 27 AMA positive/anti-M2-negative sera (52%) reacted in the WB with a 60kDa- and 8 (29%) with an 80kDa-protein, both present in the 100.000g supernatant from bovine heart mitochondria accumulating at sucrose densities 1.14-1.16. An identity of these determinants with any of the M2-related antigens could be excluded. In the 60kDa band components of the mitochondrial enzymes F1F0-ATPase, ubiquinone cytochrome C reductase and acyl CoA dehydrogenase were detected by MALDI-TOF analysis; the 80kDa protein could not be further characterized.

                Conclusions: AMA positive/anti-M2 negative PBC sera contain antibodies to further mitochondrial antigens at 60 and 80kDa which do not correspond to any of the M2-determinants. Those antibodies can be detected to a lesser extent in sera from patients with classical anti-M2 positive PBC but not in patients with other hepatic and non-hepatic disorders.

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