Natural antipig xenoantibody is absent in neonatal human serum

Background: Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the current shortage of donor organs suitable for heart allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyperacute rejection, a process thought to be mediated by natural antixenodonor antibodies. On the basis of our previous findings that cytotoxic natural xenoantibodies are immunoglobulin M in nature and that natural immunoglobulin M xenoantibodies are barely detectable in neonatal baboon serum, we postulated that immunoglobulin M xenoantibodies may be absent from newborn human serum. Methods: Neonatal human sera were obtained from the cord blood of normal term infants and pooled. Pooled adult human sera were used as a control. A whole cell enzyme-linked immunosorbent assay and a complement-mediated cytotoxicity assay were performed to determine the binding and cytotoxicity of these xenoantibodies to pig aortic endothelial cells and pig lymphocytes. Results: Neonatal human sera did not show binding of immunoglobulin M xenoantibody to pig aortic endothelial cells or lymphocytes. However, low level binding of immunoglobulin G xenoantibodies was detected to pig endothelial cells and lymphocytes. In contrast, adult human sera showed significant binding of both natural immunoglobulin M and G xenoantibodies to pig aortic endothelial cells and lymphocytes. In addition, adult human immunoglobulin M xenoantibodies bound with similar avidity to both cultured adult and neonatal pig aortic endothelial cells. Although neonatal human sera were not cytotoxic to target cells, adult sera were cytotoxic to both pig aortic endothelial cells and pig lymphocytes. Our findings indicate that neonatal human sera lack natural antipig immunoglobulin M xenoantibodies, and therefore, neonatal human serum is not cytotoxic to pig endothelial cells or lymphocytes. Like adult pig endothelial cells, neonatal pig endothelial cells may also express similar membrane xenoantigens recognized by natural immunoglobulin M xenoantibodies. Conclusions: The absence of cytotoxic natural immunoglobulin M xenoantibodies in the neonate suggests that discordant xenotransplantation may be feasible in the neonate.