NATURAL ANTIPIG XENOANTIBODY IS ABSENT IN NEONATAL HUMAN SERUM

Background: Discordant xenotransplantation represents an attractive al ternative to allotransplantation in light of the current shortage of d onor organs suitable for heart allotransplantation. Unfortunately, dis cordant 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 xenoantib odies are immunoglobulin M in nature and that natural immunoglobulin M xenoantibodies are barely detectable in neonatal baboon serum, we pos tulated that immunoglobulin M xenoantibodies may be absent from newbor n human serum. Methods: Neonatal human sera were obtained from the cor d blood of normal term infants and pooled. Pooled adult human sera wer e used as a control. A whole cell enzyme-linked immunosorbent assay an d a complement-mediated cytotoxicity assay were performed to determine the binding and cytotoxicity of these xenoantibodies to pig aortic en dothelial cells and pig lymphocytes. Results: Neonatal human sera did not show binding of immunoglobulin M xenoantibody to pig aortic endoth elial cells or lymphocytes. However, low level binding of immunoglobul in G xenoantibodies was detected to pig endothelial cells and lymphocy tes. In contrast, adult human sera showed significant binding of both natural immunoglobulin M and G xenoantibodies to pig aortic endothelia l cells and lymphocytes. In addition, adult human immunoglobulin M xen oantibodies bound with similar avidity to both cultured adult and neon atal pig aortic endothelial cells. Although neonatal human sera were n ot cytotoxic to target cells, adult sera were cytotoxic to both pig ao rtic endothelial cells and pig lymphocytes. Our findings indicate that neonatal human sera lack natural antipig immunoglobulin M xenoantibod ies, and therefore, neonatal human serum is not cytotoxic to pig endot helial cells or lymphocytes. Like adult pig endothelial cells, neonata l pig endothelial cells may also express similar membrane xenoantigens recognized by natural immunoglobulin M xenoantibodies. Conclusions: T he absence of cytotoxic natural immunoglobulin M xenoantibodies in the neonate suggests that discordant xenotransplantation may be feasible in the neonate.