FATE OF ANTIGEN IN XENOTRANSPLANTATION - IMPLICATIONS FOR ACUTE VASCULAR REJECTION AND ACCOMMODATION

Antigen down-modulation plays a critical role in xenotransplants invol ving humoral responses against the Forssman antigen and may play a rol e in the long-term survival of ABO-incompatible allografts. The presen t study investigates the fate of porcine antigens in pig-to-primate xe notransplantation. Human antibodies bound to the glycocalyx of culture d porcine aortic endothelial cells as judged by electron microscopy an d were shed from the cell surface in a complex with fibronectin, a gly coprotein that is found in the apical membrane glycocalyx of cultured cells. Antibody was shed in a metabolically dependent process with a t (1/2) of 2 to 3 hours. However, the amount of antigen on the cell surf ace did not change appreciably within 24 hours, suggesting that antige n modulation did not occur. Over the ensuing days, antigen expression decreased, although the change was always less than 50% of baseline. C hanges in antigen expression were due for the most part to changes in expression of alpha-galactosyl residues. Consistent with results obtai ned in vitro, antigen expression in porcine organ transplants remained at approximately the baseline level as determined by immunofluorescen ce analysis of IgM binding to graft endothelium. If, as these results suggest, antigen is not down-modulated in pig-to-primate xenotransplan tation, then therapies aimed at prolonged xenograft survival must focu s on antibody of genetic manipulation of antigen expression.