Primary biliary cirrhosis: an orchestrated immune response against epithelial cells

Immunol Rev. 2000 Apr;174:210-25. doi: 10.1034/j.1600-0528.2002.017402.x.


Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis. The serologic hallmark of PBC is the presence of antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex. The mechanisms by which (and if) such antibodies produce liver tissue injury are unknown. However, the presence of these antibodies has allowed detailed immunological definition of the antigenic epitopes, the nature of reactive autoantibodies and the characterization of T-cell responses. Several mechanisms may now be proposed regarding the immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and intracellular interaction between the IgA class of antimitochondrial antibodies and mitochondrial autoantigens. There are major questions which remain unanswered, including, of course, etiology, but also the reasons for female predominance, the absence of PBC in children, the relative ineffectiveness of immunosuppressive drugs, and the specific role of mitochondrial antigens. The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Acyltransferases / immunology*
  • Age Distribution
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Autoimmune Diseases / epidemiology
  • Autoimmune Diseases / immunology*
  • Bacterial Proteins / immunology
  • Bile Ducts / immunology
  • Bile Ducts / pathology
  • Cell Line
  • Cross Reactions
  • Cytokines / physiology
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Dogs
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Escherichia coli Infections / complications
  • Escherichia coli Infections / immunology
  • Female
  • Genetic Predisposition to Disease
  • HLA-D Antigens / genetics
  • HLA-D Antigens / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunoglobulin A / immunology
  • Liver Cirrhosis, Biliary / epidemiology
  • Liver Cirrhosis, Biliary / etiology
  • Liver Cirrhosis, Biliary / immunology*
  • Male
  • Maternal-Fetal Exchange
  • Middle Aged
  • Mitochondria, Liver / immunology*
  • Molecular Mimicry
  • Molecular Sequence Data
  • Peptides / immunology*
  • Pregnancy
  • Protein Structure, Tertiary
  • Pyruvate Dehydrogenase Complex / immunology*
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / pathology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sex Distribution


  • Autoantibodies
  • Autoantigens
  • Bacterial Proteins
  • Cytokines
  • HLA-D Antigens
  • Immunodominant Epitopes
  • Immunoglobulin A
  • PDHX protein, human
  • Peptides
  • Pyruvate Dehydrogenase Complex
  • Acyltransferases
  • dihydrolipoamide acyltransferase
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • dihydrolipoamide succinyltransferase