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

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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

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Biliary Liver Cirrhosis
Immunoglobulin A
Canidae
Mitochondria
Kidney
Epithelial Cells
Autoantigens
Dihydrolipoyllysine-Residue Acetyltransferase
Staining and Labeling
Autoantibodies
Autoimmune Diseases
Liver Diseases
Microscopy
Anti-Idiotypic Antibodies
Color
Immunohistochemistry
Monoclonal Antibodies
Liver
Serum

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Penetration and co-localization in MDCK cell mitochondria of IgA derived from patients with primary biliary cirrhosis. / Malmborg, Ann Christin; Shultz, David B.; Luton, Frédéric; Mostov, Keith E.; Richly, Erik; Leung, Patrick S; Benson, Gordon D.; Ansari, Aftab A.; Coppel, Ross L.; Gershwin, M. Eric; Van de Water, Judith A.

In: Journal of Autoimmunity, Vol. 11, No. 5, 10.1998, p. 573-580.

Research output: Contribution to journalArticle

Malmborg, Ann Christin ; Shultz, David B. ; Luton, Frédéric ; Mostov, Keith E. ; Richly, Erik ; Leung, Patrick S ; Benson, Gordon D. ; Ansari, Aftab A. ; Coppel, Ross L. ; Gershwin, M. Eric ; Van de Water, Judith A. / Penetration and co-localization in MDCK cell mitochondria of IgA derived from patients with primary biliary cirrhosis. In: Journal of Autoimmunity. 1998 ; Vol. 11, No. 5. pp. 573-580.
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