The role of anti-Galα1-3Gal antibodies in acute vascular rejection and accommodation of xenografts

Shu S. Lin, Michael J. Hanaway, Gonzalo V. Gonzalez-Stawinski, Christine L. Lau, William Parker, R. Duane Davis, Guerard W. Byrne, Lisa E. Diamond, John S. Logan, Jeffrey L. Platt

Research output: Contribution to journalArticlepeer-review

135 Scopus citations


Background. A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galα1-3Gal epitopes in porcine tissue, initiate this phenomenon. Methods and results. Specific depletion of anti-Galα1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide. Galα1-3Galβ1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Galα1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation. Conclusion. These results demonstrate that anti-Galα1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.

Original languageEnglish (US)
Pages (from-to)1667-1674
Number of pages8
Issue number12
StatePublished - Dec 27 2000
Externally publishedYes


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