Molecular mimicry in primary biliary cirrhosis: Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2

Judith A Van de Water, Jill Turchany, Patrick S Leung, Jack Lake, Santiago Munoz, Charles D. Surh, Ross Coppel, Attab Ansah, Yasuni Nakanuma, M. Eric Gershwin

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC.

Original languageEnglish (US)
Pages (from-to)2653-2664
Number of pages12
JournalJournal of Clinical Investigation
Volume91
Issue number6
StatePublished - Jun 1993

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Dihydrolipoyllysine-Residue Acetyltransferase
Molecular Mimicry
Biliary Liver Cirrhosis
Epithelial Cells
Immunoglobulin A
Sclerosing Cholangitis
Monoclonal Antibodies
Antibodies
Enzymes
Indirect Fluorescent Antibody Technique
Fluorescence Microscopy
Confocal Microscopy
Bile
Fluorescent Antibody Technique
Hepatocytes
Oxidoreductases
Epithelium
Immunoglobulin G
Staining and Labeling
Liver

Keywords

  • Aberrant expression
  • Autoantibodies
  • Confocal microscopy
  • IgA
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Molecular mimicry in primary biliary cirrhosis : Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2. / Van de Water, Judith A; Turchany, Jill; Leung, Patrick S; Lake, Jack; Munoz, Santiago; Surh, Charles D.; Coppel, Ross; Ansah, Attab; Nakanuma, Yasuni; Gershwin, M. Eric.

In: Journal of Clinical Investigation, Vol. 91, No. 6, 06.1993, p. 2653-2664.

Research output: Contribution to journalArticle

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abstract = "Sera from patients with primary biliary cirrhosis (PBC) react with enzymes of the 2-oxo dehydrogenase pathways, particularly PDC-E2. These enzymes are present in all nucleated cells, yet autoimmune damage is confined to biliary epithelial cells. Using a panel of eight mouse monoclonal antibodies and a human combinatorial antibody specific for PDC-E2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing cholangitis, and hepatocarcinoma. The monoclonal antibodies gave typical mitochondrial immunofluorescence on biliary epithelium and on hepatocytes from patients with either PBC, progressive sclerosing cholangitis, or hepatocarcinoma. However, one of eight mouse monoclonal antibodies (C355.1) and the human combinatorial antibody reacted with great intensity and specificity with the luminal region of biliary epithelial cells from patients with PBC. Simultaneous examination of these sections with an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be interpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial cells in PBC.",
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