Immunology of primary sclerosing cholangitis

Abstract

Primary sclerosing cholangitis is classified as an atypical autoimmune liver disease that is strongly associated with inflammatory bowel disease of the colon, principally ulcerative colitis. Multiple immunological features suggest involvement of innate and adaptive immune responses in the immunopathogenesis of peribiliary inflammation and stricturing fibrosis of intrahepatic and/or extrahepatic bile ducts. Among the immunological features are HLA associations with susceptibility and protection, a putative autoantigen and autoantibodies, and increasing evidence that gut-primed memory T cells are important effector cells of peribiliary injury, fibrous strictures, and expanding, concentric peribiliary fibrosis that displaces the peribiliary capillary plexi from the bile ducts. The impact of chronic inflammation, cytokine and chemokine production, and progressive periductal fibrosis at variable levels of the biliary tract results in ductopenia, cholestasis, and biliary obstruction culminating in secondary biliary cirrhosis.