The immunopathogenesis of primary biliary cirrhosis

There have been several recent advances in our understanding of primary biliary cirrhosis. Foremost amongst these has been the cloning and identification of the mitochondrial autoantigens as members of the 2-oxo-dehydrogenase complex. These include the E2 components of PBC, BCKD and OGDC. The immunodominant autoepitopes of the autoantigens have been mapped and, in all cases, correspond to the inner lipoyl domain. Limited progress has also been made on T cells, particularly the CD4 response. However, the fundamental mechanisms and the role, if any, of CD8 cells are unknown. Finally, at least 2 groups have identified a molecule that cross-reacts with PDC-E2, i.e., a mimic, on the luminal surface of biliary epithelium in PBC but not controls. The identification of this molecule will be critical in further understanding the immune response of this disease.