title: Immune-mediated bile duct injury: The case of primary biliary cirrhosis.
abstract: Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells. Nevertheless, the condition is universally named primary biliary cirrhosis (PBC). The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence. One twin study and numerous epidemiology reports suggest that both a susceptible genetic background and environmental factors determine disease onset while a recent genome-wide association study proposed highly significant associations with several common genetic polymorphisms in subgroups of patients. Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a genetically susceptible host, possibly through molecular mimicry. Importantly, several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria. From a pathogenetic standpoint, new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs. We are convinced that the application of the most recent molecular techniques will soon provide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics.
authors: Carlo Selmi, Pietro Invernizzi, Division of Internal Medicine and Hepatobiliary Immunopathology Unit, IRCCS Istituto Clinico Humanitas, Rozzano 20089, Italy.
authors: Carlo
authors: C
authors: Selmi
authors: Andrea
authors: A
authors: Affronti
authors: Laura
authors: L
authors: Ferrari
authors: Pietro
authors: P
authors: Invernizzi
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