Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression

Koichi Tsuneyama, Judith A Van de Water, Patrick S Leung, Sanghoon Cha, Yasuni Nakanuma, Marshall Kaplan, Ronald De Lellis, Ross Coppel, Aftab Ansari, M. Eric Gershwin

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDCE2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelial may be the earliest lesion in PBC.

Original languageEnglish (US)
Pages (from-to)1031-1037
Number of pages7
JournalHepatology
Volume21
Issue number4
DOIs
StatePublished - 1995

Fingerprint

Dihydrolipoyllysine-Residue Acetyltransferase
Biliary Liver Cirrhosis
Major Histocompatibility Complex
Epithelium
Epithelial Cells
Cholangitis
Autoantigens
Autoantibodies
Autoimmune Diseases
Liver Diseases

ASJC Scopus subject areas

  • Hepatology

Cite this

Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression. / Tsuneyama, Koichi; Van de Water, Judith A; Leung, Patrick S; Cha, Sanghoon; Nakanuma, Yasuni; Kaplan, Marshall; De Lellis, Ronald; Coppel, Ross; Ansari, Aftab; Gershwin, M. Eric.

In: Hepatology, Vol. 21, No. 4, 1995, p. 1031-1037.

Research output: Contribution to journalArticle

@article{9cc13534b90e432398b20f4c0ccafffb,
title = "Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression",
abstract = "Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDCE2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelial may be the earliest lesion in PBC.",
author = "Koichi Tsuneyama and {Van de Water}, {Judith A} and Leung, {Patrick S} and Sanghoon Cha and Yasuni Nakanuma and Marshall Kaplan and {De Lellis}, Ronald and Ross Coppel and Aftab Ansari and Gershwin, {M. Eric}",
year = "1995",
doi = "10.1016/0270-9139(95)90251-1",
language = "English (US)",
volume = "21",
pages = "1031--1037",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression

AU - Tsuneyama, Koichi

AU - Van de Water, Judith A

AU - Leung, Patrick S

AU - Cha, Sanghoon

AU - Nakanuma, Yasuni

AU - Kaplan, Marshall

AU - De Lellis, Ronald

AU - Coppel, Ross

AU - Ansari, Aftab

AU - Gershwin, M. Eric

PY - 1995

Y1 - 1995

N2 - Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDCE2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelial may be the earliest lesion in PBC.

AB - Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease characterized histologically by nonsuppurative destructive cholangitis. Sera from patients with PBC react with a series of intramitochondrial enzymes with the immunodominant response directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Recently, using tissue sections of late-stage PBC, we showed that there is increased expression in biliary epithelial cells of patients with PDCE2 or a molecule cross-reactive with PDC-E2. Previous work has shown that biliary epithelial cells of patients with PBC express an increased amount of class II. To address the sequence of events in the evolution of PBC, we have focused our attention in this study on early biliary epithelial lesions. In particular, we have studied the liver of 22 female patients with PBC that was diagnosed as either stage I or stage II using both a mouse monoclonal antibody that has reactivity similar to human autoantibodies as well as a human Fab combinatorial prepared from the lymph node of a PBC patient. Tissues were simultaneously stained using antibodies to PDC-E2, class II, and BB1/B7. As a positive control, tissues from late-stage PBC were studied concurrently. By determining the order of expression among the three molecules, PDC-E2, class II, and BB1/B7, we report that the expression of PDC-E2 or a PDC-E2-like molecule on biliary duct epithelium of patients with PBC precedes the expression of BB1/B7 and major histocompatibility complex (MHC) class II molecules. The alteration of an autoantigen in biliary duct epithelial may be the earliest lesion in PBC.

UR - http://www.scopus.com/inward/record.url?scp=0028939963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028939963&partnerID=8YFLogxK

U2 - 10.1016/0270-9139(95)90251-1

DO - 10.1016/0270-9139(95)90251-1

M3 - Article

VL - 21

SP - 1031

EP - 1037

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -