The antigenic heterogeneity of the bile duct epithelium in alcoholic liverdisease

The chronic alcoholic patient is usually immunosuppressed, but the signific ance of this phenomenon in terms of bile duct injury is unclear. The immuno reactivity of the bile duct cells was examined in a series of 69 frozen liv er biopsy specimens obtained from patients with alcoholic liver disease, co mprising 29 cases of cirrhosis, 26 of alcoholic hepatitis, 10 cases of alco holic fatty liver, and 4 specimens from normal livers. Liver diseases such as primary biliary cirrhosis and human hepatic allograft rejection, known t o have an autoimmune basis, share the characteristic feature of damage to t he bile duct epithelial cells. In both instances the damage seems to be imm une mediated, but the nature of the antigens involved is not established. W e used the avidin-biotin-peroxidase complex method to test in alcoholic liv er disease far the expression of a battery of surface antigen markers that have been incriminated in tissue injury and are usually present in lymphoid cells but also expressed by epithelium. In this study we investigated the expression of the following molecules: HLA class I (ABC) and class II (HLA- DR, HLA-DP, HLA-DQ), CD29, CD45RA, CD45RO, CD56, interleukin 1(IL-l), IL-2, IL-4, interferon (IFN-gamma), tumor necrosis factor beta, and transforming growth factor beta 1 (TGF-beta 1). The bile duct epithelial cells strongly expressed HLA-ABC in all cases, CD56 in 47 of 55, IL-4 in 15 of 41, TGF-be ta 1 in 14 of 25, and CD29 in 4 of 25 cases. The other markers including IF N-gamma, HLA-DR, HLA-DP, and HLA-DQ were not expressed by bile duct cells. The expression of HLA class I agrees with previous observations while the a bsence of class II expression does not. The expression by the bile duct epi thelium of CD56 confirms our own previous report. A new observation is the finding of molecules such as IL-4, TGF-beta 1, and CD29 strongly expressed in the bile ducts cells. The presence of these molecules, taken together wi th the lack of IFN-gamma expression, contradicts previous speculations that attributed to IFN-gamma a role in the induction of major histocompatibilit y antigens and adhesion molecules in immune-mediated alcoholic liver diseas e.