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

Ann Christin Malmborg, David B. Shultz, Frédéric Luton, Keith E. Mostov, Erik Richly, Patrick S Leung, Gordon D. Benson, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin, Judith A Van de Water

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)573-580
Number of pages8
JournalJournal of Autoimmunity
Volume11
Issue number5
DOIs
StatePublished - Oct 1998

Keywords

  • Co-localization
  • Epithelial cell
  • IgA
  • MDCK
  • PBC

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Penetration and co-localization in MDCK cell mitochondria of IgA derived from patients with primary biliary cirrhosis'. Together they form a unique fingerprint.

  • Cite this