INDUCED EXPRESSION OF HEAT-SHOCK PROTEIN ON BILIARY EPITHELIUM IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND PRIMARY BILIARY-CIRRHOSIS

In both primary sclerosing cholangitis and primary biliary cirrhosis i t is supposed that immunological mechanisms are involved in the progre ssive destruction of the bile ducts. The aberrant expression of human leukocyte antigen-DR in the bile ducts of patients with these disorder s enables the biliary epithelium to present putative antigens to the s urrounding lymphocytes; however, no such antigen has been identified. Heat-shock proteins have been implicated in the pathogenesis of variou s immunological destructive disorders. Liver biopsy specimens from pat ients with primary biliary cirrhosis (n = 10) and primary sclerosing c holangitis (n = 13) were compared with those from patients with chroni c hepatitis C infection (n = 5) and alcoholic cirrhosis (n = 4) and fr om 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 m onoclonal antibody against human leukocyte antigen-DR and with the mon oclonal antibody Identi-Tr TCR delta1, which recognizes a determinant on the delta-chain of the gamma/delta form of the human T-cell recepto r. Human leukocyte antigen-DR expression was found on the biliary epit helium of all primary sclerosing cholangitis and primary biliary cirrh osis patients but not on bile ducts from patients with alcoholic cirrh osis or chronic hepatitis C infection or those from normal controls. T he biliary epithelium reacted with ML30 in 9 of 10 primary biliary cir rhosis patients and in all primary sclerosing cholangitis patients. Tw o different patterns of epithelial staining were observed: a perinucle ar pattern and intense staining in the apical part of the cell cytopla sm, as demonstrated with confocal laser scanning microscopy. In the gr oup of patients with chronic hepatitis C infection and alcoholic cirrh osis, ML30 reactivity was less extensive and was present only around t he nuclei of bile duct cells. None of the bile ducts in the normal liv ers reacted with ML30. Staining with ML30 could not be correlated with the histological or clinical staging of the patients. The number and distribution of gamma/delta T cells did not differ between the normal liver specimens and the various patient groups. Whether the finding of an induced expression of heat-shock protein in the secretory part of the biliary epithelium in primary biliary cirrhosis and primary sclero sing cholangitis will imply that the heat-shock proteins may act as an immune target recognized by the T cells surrounding the bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis must be elucidated in further studies.