HUMORAL RESPONSES TO PIG-TO-BABOON CARDIAC TRANSPLANTATION - IMPLICATIONS FOR THE PATHOGENESIS AND TREATMENT OF ACUTE VASCULAR REJECTION AND FOR ACCOMMODATION

Organs transplanted between phylogenetically-disparate species, such a s from the pig into the primate, are subject to hyperacute and acute v ascular rejection. Hyperacute rejection of a porcine organ by a primat e is thought to be initiated by the binding of xenoreactive natural an tibodies to Gal alpha 1-3Gal expressed on the endothelial lining of bl ood vessels in the xenograft. The factor(s) which initiates acute vasc ular rejection is uncertain; however, there is some evidence implicati ng xenoreactive antibodies. The nature of the humoral response which m ight contribute to acute vascular rejection of a porcine organ was inv estigated in baboons which received a porcine cardiac xenograft plus i mmunosuppression with methylprednisolone, azathioprine and cyclosporin e. Following rejection and surgical removal of the xenografts, the ser um concentration of xenoreactive antibodies increased in untreated ani mals but in immunosuppressed animals was similar to the concentration in preimmune serum. The antibodies in the sensitized recipients were s pecific for Gal alpha 1-3Gal (70-95%) and other determinants (5-30%). However, cross-blocking studies showed that, following xenotransplanta tion, the immunosuppressed baboons had no detectable IgM or IgG direct ed against ''new'' endothelial antigens. These results indicate that a ntibodies made by immunosuppressed individuals in response to xenotran splantation are much like xenoreactive natural antibodies and suggest that acute vascular rejection might in some cases be addressed by ther apeutic strategies antibodies. (C) American Society for Histocompatibi lity and Immunogenetics, 1997, Published by Elsevier Science Inc.