Expression of CD44 on bile ducts in primary sclerosing cholangitis and primary biliary cirrhosis

Aim-To examine expression of CD44, a transmembrane glycoprotein involved in lymphocyte homing and activation, in inflammatory liver diseases. Methods-Formalin fixed, paraffin embedded tissues were obtained from normal , uninvolved liver from patients undergoing partial hepatectomy for meta-st atic carcinoma (9) and transplant hepatectomy specimens from patients with primary biliary cirrhosis (12), primary sclerosing cholangitis (8), autoimm une hepatitis (3), hepatitis C (3), and secondary sclerosing cholangitis (1 ), Expression of CD44 (using antibodies to three core epitopes), HLA-DR, an d lymphocyte phenotypic markers was studied by immunohistochemistry. Results-CD44 expression was not detected in either hepatocytes or biliary e pithelial cells in normal livers. In sections from all 27 transplant hepate ctomy specimens, CD44 was positive in bile duct epithelial cells but not in hepatocytes. The proportion of CD44, ducts was much higher in biliary dise ase than in chromic hepatitis. By contrast, expression of HLA-DR was detect ed in a relatively small percentage of bile ducts. Activated, memory phenot ype CD4(+) T lymphocytes were increased in the parenchyma of all diseased l ivers and an infiltrate of activated CD8(+) cells within the biliary epithe lium was evident in inflammatory biliary disease. Conclusions-CD44 appears to play an important role in the development of au toimmune biliary disease by promoting lymphoepithelial interactions, wherea s HLA-DR may be involved in the subsequent progression of these conditions.