THE ROLE OF NATURAL ANTI-GAL-ALPHA-1-3GAL ANTIBODIES IN HYPERACUTE REJECTION OF PIG-TO-BABOON CARDIAC XENOTRANSPLANTS

Xenoreactive natural antibodies in humans and higher primates are dire cted predominantly at Gal alpha 1-3Gal. These antibodies are thought t o Initiate hyperacute rejection of porcine organ xenografts. The contr ibution of anti-Gal alpha 1-3Gal antibodies to the xenoreactive natura l antibody repertoire and to the initiation of hyperacute rejection wa s tested in a pig-to-baboon cardiac xenograft model. Anti-Gal alpha 1- 3Gal antibodies were depleted from baboons by extracorporeal absorptio n of anti-Gal alpha 1-3Gal antibodies from plasma using columns with a matrix bearing Gal alpha 1-3Galb1-4GlcNAc. Specific removal of anti-G al alpha 1-3Gal antibodies mas achieved prior to transplantation as de monstrated by immunoassay. Porcine hearts were then transplanted into these baboons and the outcome of the transplants sas analysed. Immunof luorescence revealed little deposition of baboon antibodies in the gra fts. The porcine hearts did not undergo hyperacute rejection even thou gh complement activity was similar to 90% of baseline at the time of t ransplantation. These findings demonstrate that anti-Gal alpha 1-3Gal antibodies constitute a major fraction of xenoreactive natural antibod ies in primate blood and that these antibodies contribute significantl y to the pathogenesis of hyperacute xenograft rejection.