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 t he E2 subunit of the pyruvate dehydrogenase complex (PDC-E2) on biliar y epithelial cells in patients with primary biliary cirrhosis (PBC) bu t not primary sclerosing cholangitis. This distribution has been demon strated using a mouse monoclonal antibody, coined C355.1. The epitope recognized by C355.1 is near the lipoic acid binding site of PDC-E2. C 355.1 inhibits PDC-E2 activity in vitro and, unlike a panel of other m onoclonal antibodies against different regions of PDC-E2, appears to b ind not only to mitochondria hut also to a unique antigen expressed pr edominantly on the luminal side of biliary epithelial cells in PBC. We have extended these observations by studying the subcellular reactivi ty of C355.1 using postembedding immunoelectron microscopy on the intr ahepatic small bile ducts of PBC livers, extrahepatic biliary obstruct ion (EBO) livers, and normal livers. We report that the reactivity of C355.1 can be classified into two categories. The first category is ch aracterized by small foci of reaction products that were randomly disp ersed in cytoplasm, particulary in supranuclear areas; the ultrastruct ural characterization of these foci H-as 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 reac tion products around the biliary lumen, including microvilli and adjac ent 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 furt her define and highlight the unique subcellular distribution of PDC-E2 around the biliary lumen in PBC livers and suggest that this abnormal ity is related to the pathogenesis of bile duct lesions. HUM PATHOL 26 :92-98. Copyright (C) 1995 by W.B. Saunders Company