Formation of immune complexes after organ xenotransplantation
The rejection of organ xenografts is initiated when natural antibodies of the recipient bind to donor endothelium, activating the complement cascade and leading to changes in vascular endothelial cells. This sequence of events is typical of a Type II, or cytotoxic immune reaction. While Type II reactions clearly occur in organ xenografts, experiments in pulmonary xenotransplantation from pig to baboon suggest that deposition of antibody and complement in the graft might be different from other organs. We asked whether different immunochemical reactions might occur following pulmonary xenotransplantation compared to renal and cardiac xenotransplantation. We tested this concept in baboons, which had received porcine pulmonary, renal, or cardiac xenotransplants or in porcine lungs, kidneys and hearts perfused with blood from baboons. After xenotransplantation and perfusion, the blood of baboons was found to contain high molecular weight complexes consisting of baboon IgM and porcine von Willebrand factor. The baboon IgM in these complexes was specific for Galα1-3Gal. Possibly because of the large vascular surface of the lung, these complexes were found in greater amounts after pulmonary xenotransplantation than after renal or cardiac xenotransplantation. Deposits of porcine von Willebrand factor and baboon C3 were detected in the livers and spleens of transplanted baboons. The kidneys of baboons, which had received pulmonary xenotransplants, also had deposits of porcine von Willebrand factor. These results indicate that pulmonary xenotransplantation and, to a lesser extent, renal and cardiac xenotransplantation, lead to a Type III immune reaction, i.e. the formation of immune complexes, and that these complexes deposit at distant sites. Immune complex formation might contribute to systemic changes not previously considered a complication of xenotransplantation and to sensitization of xenotransplant recipients.