Induced expression of heat-shock protein on biliary epithelium in patients with primary sclerosing cholangitis and primary biliary cirrhosis

Abstract

In both primary sclerosing cholangitis and primary biliary cirrhosis it is supposed that immunological mechanisms are involved in the progressive destruction of the bile ducts. The aberrant expression of human leukocyte antigen-DR in the bile ducts of patients with these disorders enables the biliary epithelium to present putative antigens to the surrounding lymphocytes; however, no such antigen has been identified. Heat-shock proteins have been implicated in the pathogenesis of various immunological destructive disorders. Liver biopsy specimens from patients with primary biliary cirrhosis (n = 10) and primary sclerosing cholangitis (n = 13) were compared with those from patients with chronic hepatitis C infection (n = 5) and alcoholic cirrhosis (n = 4) and from normal controls (n = 6). Liver sections were investigated by means of immunohistochemical study using a mouse monoclonal antibody, ML30, directed against the 65-kD heat-shock protein of Mycobacterium, with monoclonal antibody against human leukocyte antigen-DR and with the monoclonal antibody Identi-Tr TCR delta 1, which recognizes a determinant on the delta-chain of the gamma/delta form of the human T-cell receptor. Human leukocyte antigen-DR expression was found on the biliary epithelium of all primary sclerosing cholangitis and primary biliary cirrhosis patients but not on bile ducts from patients with alcoholic cirrhosis or chronic hepatitis C infection or those from normal controls. The biliary epithelium reacted with ML30 in 9 of 10 primary biliary cirrhosis patients and in all primary sclerosing cholangitis patients.(ABSTRACT TRUNCATED AT 250 WORDS)