Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the shortage of donor organs currently available for cardiac allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyperacute rejection, a process thought to be mediated by natural anti-xenodonor antibody. Based on data that cytotoxic natural xenoantibodies are IgM in nature, we postulated that natural xenoantibodies may be absent from newborn serum. Baboon sera were collected from infant baboons. Pooled adult baboon sera were used as controls. A whole cell ELISA was performed to determine the binding of xenoantibodies to pig aortic endothelial cells and pig lymphocytes. The cytotoxicity of both adult and newborn baboon sera to pig aortic endothelial cells was measured by a MTT (3-(4,5-dimethyl-thiazoyl-2-y) 2,5 diphenyl-tetrazolium bromide) assay. Newborn baboon sera demonstrated very low levels of binding of natural IgM xenoantibodies to pig endothelial cells and lymphocytes, whereas natural IgM xenoantibodies from adult baboon sera bound significantly to both pig aortic endothelial cells and lymphocytes. IgG natural antibodies in both adult and newborn sera bound to pig endothelial cells and pig lymphocytes. The MTT assay demonstrated high levels of cytotoxicity to pig endothelial cells from adult baboon sera and very low levels of cytotoxicity from newborn baboon sera. In this study, newborn baboon sera were demonstrated to be free of natural IgM xenoantibodies to pig endothelial cells and lymphocytes. Although natural anti-pig IgG antibodies were present in newborn sera, newborn baboon sera lack cytotoxicity to pig target cells. These findings suggest that IgM is the more important xenoantibody and that hyperacute rejection of discordant cardiac xenografts may be avoidable in the newborn.
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