Immunopathogenesis of Primary Sclerosing Cholangitis

Abstract

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology;however, lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for PSC. Associations with inflammatory bowel disease--especially ulcerative colitis--and with other auto-immune diseases, together with genetic associations, further suggest that PSC may be an immune-mediated disease. The immunogenetics of PSC have been the subject of active research, and several human leukocyte antigen (HLA)- and non-HLA-associated genes have been implicated in the development of the disease. Lymphocytes derived from the inflamed gut may enter the liver via the enterohepatic circulation to cause hepatic disease.PSC may be triggered in genetically susceptible individuals by infections or toxins entering the portal circulation through a permeable colon and, therefore, evoking an abnormal immune response.

Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease

“…3, A-C, right). Changes in ALT and p-ANCA have been associated with the development of chronic liver and colon inflammation, including AIH and PSC (52,54,61).…”

Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis ‐ a pilot study

“…[19][20][21][22][23] Further supporting the PSC microbiota hypothesis is the observation, for example, that patients with PSC often have a leucocyte differential exhibiting increased neutrophils, even in the absence of signs or symptoms of acute cholangitis, suggesting circulation of endotoxins or other immunoactive molecules. 24 Collectively, these and animal model 25,26 findings point toward a role for bacteria and bacterially derived molecules in the aetiopathogenesis of PSC.…”

Comparative assessment of prognostic value for revised-mayo risk model and child-pugh score in patients with primary sclerosing cholangitis

“…There is an increasing body of evidence that immunopathogenetic mechanisms are possibly involved in PSC because of the association with human leukocyte antigen (HLA) complex haplotypes, multiple autoantibodies, and the presence of inflammatory bowel disease (IBD) in >80% of patients. However, PSC lacks the features of a typical autoimmune disease and responds poorly to immunosuppressive therapies (5)(6)(7)(8)(9)(10).…”