title: The Immunogenetics of Autoimmune Cholestasis.
abstract: The immune-mediated hepatobiliary diseases, primary biliary cirrhosis and primary sclerosing cholangitis are relatively rare, albeit and account for a significant amount of liver transplant activity and liver-related mortality globally. Precise disease mechanisms are yet to be described although a contributory role of genetic predisposition is firmly established. In addition to links with the major histocompatibility complex, a number of associations outside this region harbor additional loci which underscore the fundamental role of breaks in immune tolerance and mucosal immunogenicity in the pathogenesis of autoimmune biliary disease. We provide an overview of these key discoveries before discussing putative avenues of therapeutic exploitation based on existing findings.
authors.affiliation: National Institute of Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Wolfson Drive, Birmingham B15 2TT, UK.
authors.forename: Palak J
authors.initials: PJ
authors.lastname: Trivedi
authors.affiliation: National Institute of Health Research (NIHR) Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Wolfson Drive, Birmingham B15 2TT, UK. Electronic address: g.hirschfield@bham.ac.uk.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D015209:Cholangitis, Sclerosing / Q000235:genetics* / Q000276:immunology*; D044127:Epigenesis, Genetic; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007125:Immunogenetics; D007413:Intestinal Mucosa / Q000276:immunology*; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006680:HLA Antigens; D014409:Tumor Necrosis Factor-alpha
keywords: Autoimmune liver disease; Autoimmunity; Mucosal immunity; Primary biliary cirrhosis; Primary sclerosing cholangitis