Immune complex formation after xenotransplantation - Evidence of type III as well as type II immune reactions provide clues to pathophysiology

Rejection of renal and cardiac xenografts is initiated when natural antibod ies of the recipient bind to donor endothelium, activating complement on th e surface of endothelial cells. Pulmonary xenotransplants, however, reveal less evidence of antibody binding and complement activation and, in contras t to other xenografts, fare worse when the complement of the graft recipien t is depleted. Accordingly, we asked whether distinct immunochemical reacti ons might occur after xenotransplantation of the lung and what implications such reactions might have for pulmonary pathophysiology, Analysis of serum from baboons after transplantation with porcine lungs revealed complexes c ontaining baboon IgM and porcine von Willebrand factor. The baboon IgM in t hese complexes was specific for Gal alpha1-3Gal. Immune complexes were also seen, albeit to a lesser extent, in the serum of kidney and heart xenotran splant recipients. Deposits of porcine von Willebrand factor and baboon C3 were detected in livers and spleens of transplanted baboons. These results Indicate pulmonary xenotransplantation eventuates in formation of immune co mplexes and in the deposition of those complexes at distant sites. Immune c omplex formation could explain the peculiar fate of xenoreactive antibodies after pulmonary xenotransplantation and might contribute to the pathophysi ology of the lung and systemic changes not previously considered a complica tion of xenotransplantation.