Addison's other disease: primary biliary cirrhosis as a model autoimmune disease.
Thomas Addison described three of the classical autoimmune diseases, so can justifiably be regarded as one of the fathers of the study of autoimmunity. The least well recognised of these conditions, the autoimmune liver disease primary biliary cirrhosis (PBC), is in some ways the most interesting. As a result of the relatively advanced state of knowledge of its immunopathogenesis, it represents a good model for the study of autoimmune disease. The classical pathological lesion of PBC is apoptotic damage to the biliary epithelial cells lining the small intrahepatic bile ducts. The disease is typified by two symptom sets: fatigue and pruritus, which can occur at any stage of the disease process, and the features of advanced liver disease, which occur when secondary liver damage results from bile retention. Although autoantibodies directed at, in particular, pyruvate dehydrogenase complex (PDC) are almost universally present in PBC (and represent an important diagnostic tool), it appears likely that CD8+ cytotoxic T cells reactive with self-PDC derived epitopes are directly responsible for target cell damage. Recent studies in humans and a novel murine disease model have shed light on the mechanism of breakdown of immune tolerance to self-PDC; they provide important insights into the pathogenesis of PBC in particular and of autoimmunity in general.
Jones
David E J
DE
Centre for Liver Research, University of Newcastle, Newcastle-upon-Tyne. D.E.J.Jones@ncl.ac.uk
D000818:Animals; D006801:Humans; D007108:Immune Tolerance; D008105:Liver Cirrhosis, Biliary / Q000276:immunology* / Q000473:pathology; D023421:Models, Animal; D008954:Models, Biological; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology
D011768:Pyruvate Dehydrogenase Complex