A clinicopathologic study of isolated intestinal allografts with preformed IgG lymphocytotoxic antibodies

Abstract

Humoral rejection of human small bowel allografts has not been well documented. The aim of this study was to determine the significance of preformed IgG lymphocytotoxic antibodies, as determined by the modified Amos crossmatch technique, in 6 of 28 (21.4%) adult isolated intestinal allograft recipients treated with tacrolimus basal immunosuppression. The crossmatch with dithiothreitol (DTT) was strongly positive in 5 grafts and weakly positive in the remaining one. The strongly positive crossmatch grafts (n = 5) developed severe mucosal injuries immediately after reperfusion. Within the first 10 days after transplantation, 3 of the 5 strongly positive crossmatch grafts developed clinically and endoscopically documented severe mucosal congestion, cyanotic discoloration, and focal hemorrhage within the allograft. Simultaneous mucosal biopsy specimens demonstrated severe congestion, neutrophilic margination, and fibrin-platelet thrombi within the lamina propria microvasculature, along with focal hemorrhage, but with no histological neutrophilic or necrotizing arteritis, and the immunofluorescent findings were unremarkable. The other 2 strongly positive crossmatch allograft recipients developed macroscopic congestion of mucosa with microscopic foci of congestion and hemorrhage. In contrast, the recipient with a weakly positive crossmatch, as well as the 22 crossmatch negative recipients, exhibited none of these characteristic clinical, endoscopic, or microscopic findings ( P < .05). With prompt augmentation of the immunosuppression therapy, the 3 grafts with the characteristic clinicopathologic syndrome were successfully reversed with the monoclonal antilymphocyte preparation OKT3. Thus there was no statistical difference ( P > .05) in early graft survival and the frequency of acute rejection episodes between the crossmatch-positive and the crossmatch-negative groups within the first 6 months after transplantation. We conclude that preformed IgG lymphocytotoxic antibodies in isolated intestinal recipients can be associated with a characteristic clinicopathologic syndrome during the early postoperative course, similar to that observed in experimental animal models and in other solid organ transplantation. If recognized and treated aggressively, early graft failure can be avoided. The long-term significance of these preformed antibodies has yet to be determined.