THE HUMORAL IMMUNE-RESPONSE IN HUMANS FOLLOWING CROSS-PERFUSION OF PORCINE ORGANS

A major question in xenotransplantation is the nature of the humoral r esponse that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could med iate delayed types of injury to the graft. To begin to address this is sue we characterized the changes in the properties of xenoreactive ant ibodies occurring in patients exposed to porcine organs under conditio ns simulating transplantation. In two patients whose blood had been cr oss-perfused through porcine livers as a treatment for hepatic failure , the titer of xenoreactive IgM increased by four-fold and the titer o f xenoreactive IgG increased by sixty-fold within ten days after perfu sion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells an d bovine thyroglobulin, which express this determinant, and on the dec rease in binding following treatment of porcine endothelial cells or b ovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-bi nding sites obtained before and ten days after perfusion of porcine or gans revealed no increase in binding of IgM above the level observed w ith serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to po rcine endothelial cells of IgM in serum obtained before and ten days a fter perfusion of porcine organs was unchanged, Even at later times, t he presence of newly elicited antibodies against porcine aortic endoth elial cell targets was not detected. Thus, exposure to porcine antigen s in a vascularized organ results in increases in the levels of xenore active IgM and IgG antibodies-however, these antibodies exhibit proper ties similar to natural antibodies.