Immunopathogenesis of primary biliary cirrhosis

Akiyoshi Nishio, Emmet B. Keeffe, M. Eric Gershwin

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Although the autoantigens of antimitochondrial antibodies (AMA) have been defined and epitope mapped for both autoreactive B and T cells, the pathogenesis of primary biliary cirrhosis (PBC) still remains a mystery. The data gathered so far address several important aspects of this intriguing puzzle. First, biliary epithelial cells (BECs) seem to be immunologically active because they express molecules such as major histocompatibility complex (MHC) antigens, and adhesion and costimulatory molecules. Second, although pyruvate dehydrogenase complex (PDC)-E2, the major autoantigen in PBC, is upregulated in BECs when examined immunohistochemically, this abnormal staining seems to be secondary to immune complexes of AMA bound to PDC-E2 present in the BECs. Third, in addition to CD4+ T cells, CD8+ T cells also recognize the inner lipoyl domain of PDC-E2. Fourth, modification of mitochondrial antigens by xenobiotics may lead to the induction of the disease. These findings help to clarify the pathogenic mechanism of PBC and suggest that (1) induction may be secondary to a primary response to a xenobiotic that is normally metabolized in an estrogen-dependent pathway and (2) pathology is mediated by and orchestrated by a highly directed and specific CD4, CD8 and autoantibody response to the lipoyl domain of the mitochondrial autoantigens, with tissue destruction based on the immunoglobulin A (IgA) receptor, apoptosis, and the mucosal organization of biliary and salivary duct cells.

Original languageEnglish (US)
Pages (from-to)291-302
Number of pages12
JournalSeminars in Liver Disease
Volume22
Issue number3
DOIs
StatePublished - Aug 2002

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Dihydrolipoyllysine-Residue Acetyltransferase
Biliary Liver Cirrhosis
Autoantigens
Epithelial Cells
Xenobiotics
T-Lymphocytes
Salivary Ducts
Histocompatibility Antigens
Antibodies
Antigen-Antibody Complex
Major Histocompatibility Complex
Autoantibodies
Immunoglobulin A
Epitopes
Estrogens
B-Lymphocytes
Apoptosis
Pathology
Staining and Labeling
Antigens

Keywords

  • Molecular mimicry
  • Primary biliary cirrhosis
  • T cells
  • Xenobiotics

ASJC Scopus subject areas

  • Hepatology

Cite this

Immunopathogenesis of primary biliary cirrhosis. / Nishio, Akiyoshi; Keeffe, Emmet B.; Gershwin, M. Eric.

In: Seminars in Liver Disease, Vol. 22, No. 3, 08.2002, p. 291-302.

Research output: Contribution to journalArticle

Nishio, Akiyoshi ; Keeffe, Emmet B. ; Gershwin, M. Eric. / Immunopathogenesis of primary biliary cirrhosis. In: Seminars in Liver Disease. 2002 ; Vol. 22, No. 3. pp. 291-302.
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