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- W2005889847 abstract "Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease in which an immune‐mediated injury targets the small intrahepatic bile ducts. PBC is further characterized by highly specific serum antimitochondrial autoantibodies (AMAs) and autoreactive T cells, a striking female predominance, a strong genetic susceptibility and a plethora of candidate environmental factors to trigger the disease onset. For these reasons, PBC appears ideal to represent the developments of the clonal selection theory over the past decades. First, a sufficiently potent autoimmunogenic stimulus in PBC would require the coexistence of numerous pre‐existing conditions (mostly genetic, as recently illustrated by genome‐wide association studies and animal models) to perpetuate the destruction of the biliary epithelium by the immune system via the persistence of forbidden clones. Second, the proposed modifications of mitochondrial autoantigens caused by infectious agents and/or xenobiotics well illustrate the possibility that peculiar changes in the antigen structure and flexibility may contribute to tolerance breakdown. Third, the unique apoptotic features shown for cholangiocytes are the ideal setting for the development of mitochondrial autoantigen presentation to the immune system through macrophages and AMA; thus, turning the non‐traditional mitochondrial antigen into a traditional one. This article will review the current knowledge on PBC etiology and pathogenesis in light of the clonal selection theory developments." @default.
- W2005889847 created "2016-06-24" @default.
- W2005889847 creator A5003030575 @default.
- W2005889847 creator A5029678899 @default.
- W2005889847 creator A5073399902 @default.
- W2005889847 date "2010-10-26" @default.
- W2005889847 modified "2023-09-26" @default.
- W2005889847 title "The autoimmunity of primary biliary cirrhosis and the clonal selection theory" @default.
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