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(American Journal of Pathology. 2001;158:627-637.)
© 2001 American Society for Investigative Pathology

Regular Article

Immune Complex Formation after Xenotransplantation

Evidence of Type III as well as Type II Immune Reactions Provide Clues to Pathophysiology

Zoie E. Holzknecht^*, Sarah Coombes^*, Brian A. Blocher, Timothy B. Plummer^*, Matilde Bustos, Christine L. Lau, R. Duane Davis and Jeffrey L. Platt^*§

From the Departments of Surgery^*
and Immunology and Pediatrics,^§
Mayo Clinic, Rochester, Minnesota; the Department of Surgery,
Duke University Medical Center, Durham, North Carolina; and the Universidad de Navarra,
Pamplona, Spain

Rejection of renal and cardiac xenografts is initiated when natural antibodies of the recipient bind to donor endothelium, activating complement on the surface of endothelial cells. Pulmonary xenotransplants, however, reveal less evidence of antibody binding and complement activation and, in contrast to other xenografts, fare worse when the complement of the graft recipient is depleted. Accordingly, we asked whether distinct immunochemical reactions 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 containing baboon IgM and porcine von Willebrand factor. The baboon IgM in these complexes was specific for Gal1-3Gal. Immune complexes were also seen, albeit to a lesser extent, in the serum of kidney and heart xenotransplant 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 complexes and in the deposition of those complexes at distant sites. Immune complex formation could explain the peculiar fate of xenoreactive antibodies after pulmonary xenotransplantation and might contribute to the pathophysiology of the lung and systemic changes not previously considered a complication of xenotransplantation.

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