Are preformed antibodies to biliary epithelial cells of clinical importance in liver transplantation?

Abstract

During acute liver allograft rejection, most of the tissue damage to bile duct epithelium is thought to occur as a consequence of direct immunologic injury by T-cell-mediated immune effector mechanisms. However, the role of antibodies to biliary epithelial cells (BECs) in liver transplant rejection is not known. We therefore investigated cross-match sera obtained immediately before liver transplantation from 95 patients for the presence of BEC-reactive antibodies to determine their association with acute rejection. BECs were isolated from one normal healthy liver. Antibody binding was detected by using flow cytometric analysis. Donor lymphocyte-specific cross-matches using complement-dependent cytotoxicity (CDC) and flow cytometric assays also were performed. The 2-year patient survival rate in this study was 86.3%. Eleven patients were positive for either CDC or flow cytometric cross-matches. BEC antibodies were detected in 41 serum samples (43.2%). Patients with BEC antibodies experienced acute rejection more frequently (65.9%) compared with 42.5% without antibodies (P <.03). HLA specificity determinations indicated that in 5 of 41 cases, anti-BEC reactivity was caused by HLA antibodies. No correlations between the presence of BEC antibodies and patient survival and the occurrence of cholangitis and nonsurgical bile duct strictures were found within 2 years of follow-up. In conclusion, preformed antibodies to BECs are associated with acute rejection. Thus, the presence of these antibodies before transplantation may facilitate acute liver graft rejection.