Penetration and co-localization in MDCK cell mitochondria of IgA derived from patients with primary biliary cirrhosis

J Autoimmun. 1998 Oct;11(5):573-80. doi: 10.1006/jaut.1998.0220.


Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease of unknown etiology characterized by high-titer anti-mitochondrial antibodies. The major autoantigen has been identified as the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). The fact that PDC-E2 is present in all nucleated cells, but autoimmune damage is confined to biliary epithelial cells, prompted us to investigate the possibility that mucosally-derived IgA may be pathogenic for biliary epithelial cells. Serum IgA was purified from six patients with PBC and its localization and ability to penetrate cells was studied using Madine-Darby canine kidney (MDCK) cells transfected with the human IgA receptor (MDCK-pIgR). The potential of IgA to be transported through the cells was studied by a combination of immunohistochemistry and dual color fluorescent microscopy. Interestingly, IgA from all PBC patients co-localized with PDC-E2 (the major autoantigen of PBC) inside the cells; this was demonstrated by dual staining with anti-human IgA and a mouse monoclonal antibody directed to PDC-E2. In contrast, no co-localization was observed for IgA controls. Furthermore, dual staining of liver sections from PBC patients demonstrated co-localization of IgA and PDC-E2, both cytoplasmically and at the apical surface. We postulate that there may be a direct effect of these autoantibodies on the mitochondrial function of biliary epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens
  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / immunology*
  • Biological Transport, Active
  • Case-Control Studies
  • Cell Line
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Dogs
  • Humans
  • Immunoglobulin A / metabolism*
  • In Vitro Techniques
  • Liver / immunology
  • Liver Cirrhosis, Biliary / enzymology
  • Liver Cirrhosis, Biliary / immunology*
  • Mice
  • Microscopy, Fluorescence
  • Mitochondria / enzymology
  • Mitochondria / immunology*
  • Pyruvate Dehydrogenase Complex / immunology
  • Pyruvate Dehydrogenase Complex / metabolism
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism
  • Transfection


  • Autoantigens
  • IgA receptor
  • Immunoglobulin A
  • Pyruvate Dehydrogenase Complex
  • Receptors, Fc
  • Dihydrolipoyllysine-Residue Acetyltransferase