Primary biliary cirrhosis: a multi-faced interactive disease involving genetics, environment and the immune response

Authors

  • Raivo Uibo,

    1. Institute of General and Molecular Pathology, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia
    2. Estonian Academy of Sciences, Tallinn, Estonia
    Search for more papers by this author
  • Kai Kisand,

    1. Institute of General and Molecular Pathology, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia
    Search for more papers by this author
  • Chen-Yen Yang,

    1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA
    Search for more papers by this author
  • M. Eric Gershwin

    1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA
    Search for more papers by this author

Raivo Uibo, University of Tartu, Ravila 19, Tartu 50411, Estonia. e-mail: raivo.uibo@ut.ee

Abstract

Primary biliary cirrhosis (PBC) is considered a model autoimmune disease based on several features, including the presence of a highly directed and very specific immune response to mitochondrial autoantigens, a female predominance, a targeted destruction of the biliary epithelium, and homogeneity between patients. It is essentially a chronic progressive cholestatic liver disease characterized by immune-mediated destruction of small- and medium-sized intrahepatic bile ducts. There is considerable variation in the incidence and prevalence of the disease between regions of the world, although such differences likely reflect not only a true disparity in disease but also differences in awareness; for example, in the United States, PBC is often detected in an asymptomatic stage based on multi-phasic clinical testing. There has been considerable progress at defining the immune response in this disease, including quantitation of autoreactive T cells against PDC-E2, the major mitochondrial autoantigen. The overwhelming data suggests that patients develop PBC based on a genetic predisposition and loss of tolerance to one or more environmental agents. In this review, we will present an updated overview of PBC and place it in the context of autoimmunity.

Ancillary