Biliary epithelial expression of pyruvate dehydrogenase complex in primary biliary cirrhosis: an immunohistochemical and immunoelectron microscopic study.

It has been reported recently that there is a unique distribution of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) on biliary epithelial cells in patients with primary biliary cirrhosis (PBC) but not primary sclerosing cholangitis. This distribution has been demonstrated using a mouse monoclonal antibody, coined C355.1. The epitope recognized by C355.1 is near the lipoic acid binding site of PDC-E2. C355.1 inhibits PDC-E2 activity in vitro and, unlike a panel of other monoclonal antibodies against different regions of PDC-E2, appears to bind not only to mitochondria but also to a unique antigen expressed predominantly on the luminal side of biliary epithelial cells in PBC. We have extended these observations by studying the subcellular reactivity of C355.1 using postembedding immunoelectron microscopy on the intrahepatic small bile ducts of PBC livers, extrahepatic biliary obstruction (EBO) livers, and normal livers. We report that the reactivity of C355.1 can be classified into two categories. The first category is characterized by small foci of reaction products that were randomly dispersed in cytoplasm, particularly in supranuclear areas; the ultrastructural characterization of these foci was impossible to define but was similar in PBC and EBO. However, of particular interest was the second category of reactivity, which was characterized by deposition of reaction products around the biliary lumen, including microvilli and adjacent subluminal ectoplasm and secretory substances in the biliary lumen. This staining pattern was frequent in PBC livers, only occasionally evident in EBO livers, and not found in normal livers. These data further define and highlight the unique subcellular distribution of PDC-E2 around the biliary lumen in PBC livers and suggest that this abnormality is related to the pathogenesis of bile duct lesions.