Immunopathogenesis of primary sclerosing cholangitis: possible role of a shared colonic and biliary epithelial antigen

Abstract

Abstract Primary sclerosing cholangitis (PSC) is a chronic fibrosing disease of both extrahepatic as well as intrahepatic bile ducts that is strongly associated with inflammatory bowel disease, particularly ulcerative colitis. It is characterized by progressive destruction of the bile ducts leading to widespread biliary obstructions and biliary cirrhosis. PSC is currently one of the more common indications for liver transplantation. It is an immune mediated disorder associated with autoantibodies against both colon epithelium as well as biliary epithelium, infiltration of the portal tract with functional T cells, abnormal expression of HLA molecules on biliary epithelial cells and a restricted T‐cell receptor repertoire. Activation of the complement system, following the deposition of antigen‐specific autoantibody with biliary epithelial cells, may also contribute to the pathogenesis of PSC. Four different HLA haplotypes have been associated with PSC: three with increased risk of disease and one with reduced risk. Bacterial products entering the biliary epithelium from colon may be a triggering factor strongly associated with ulcerative colitis; however, a further immune mediated chronic inflammation may be associated with cellular antigen(s) which is shown to be shared by human colon and biliary epithelium by molecular mimicry.