MOLECULAR MIMICRY IN PRIMARY BILIARY-CIRRHOSIS - EVIDENCE FOR BILIARYEPITHELIAL EXPRESSION OF A MOLECULE CROSS-REACTIVE WITH PYRUVATE-DEHYDROGENASE COMPLEX-E2

Sera from patients with primary biliary cirrhosis (PBC) react with enz ymes of the 2-Oxo dehydrogenase pathways, particularly PDC-E2. These e nzymes are present in all nucleated cells, yet autoimmune damage is co nfined to biliary epithelial cells. Using a panel of eight mouse monoc lonal antibodies and a human combinatorial antibody specific for PDC-E 2, we examined by indirect immunofluorescence and confocal microscopy sections of liver from patients with PBC, progressive sclerosing chola ngitis, and hepatocarcinoma. The monoclonal antibodies gave typical mi tochondrial immunofluorescence on biliary epithelium and on hepatocyte s from patients with either PBC, progressive sclerosing cholangitis, o r hepatocarcinoma. However, one of eight mouse monoclonal antibodies ( C355.1) and the human combinatorial antibody reacted with great intens ity and specificity with the luminal region of biliary epithelial cell s from patients with PBC. Simultaneous examination of these sections w ith an antiisotype reagent for human IgA revealed high IgA staining in the luminal region of biliary epithelial cells in patients with PBC. IgG and IgA antibodies to PDC-E2 were detected in the bile of patients with PBC but not normal controls. We believe that this data may be in terpreted as indicating that a molecule cross-reactive with PDC-E2 is expressed at high levels in the luminal region of biliary epithelial c ells in PBC.