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Presenter: Alexander, Albritton, Boston, United States
Authors: Alexander Albritton1,3, Angelo Leto Barone1,2, Josef Kurtz1,3, Christopher Mallard1, David Sachs1, Curtis Cetrulo1,2
Alexander Albritton1,3, Angelo Leto Barone1,2, Josef Kurtz1,3, Christopher Mallard1, David Sachs1, Curtis Cetrulo1,2
1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School; 2Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School; 3Emmanuel College; Boston, MA, USABackground: The best current substitute for autologous skin grafts for temporary coverage of deep burns is skin from allogeneic donors. We have previously described the use of skin from a-1,3-galactosyltransferase knockout (GalT-KO) swine as an alternative to allografts. We have now investigated whether GalT-KO skin transplantation elicits a cross-reactive anti-allogeneic humoral response in baboons.
Methods: Baboons received primary xenogeneic and allogeneic split thickness skin grafts followed by secondary xeno and allo skin grafts from the same donors, with no immunosuppression. The development of specific anti-allo and anti-xeno IgM and IgG antibodies was assessed in the serum of the recipients by flow cytometry.
Results: In a recipient that received primary allo, xeno (Gal+) and xeno (GalT-KO) skin grafts, the Gal+ graft was rejected in a hyperacute manner, while both allo and GalT-KO grafts were rejected on day 10. Secondary allo and GalT-KO skin grafts were both rejected in an accelerated fashion, demonstrating presensitization to both allo and xeno antigens. To assess whether an anti-xeno non-Gal antibody response can accelerate rejection of an allograft, we transplanted a GalT-KO skin graft onto a naïve baboon and followed it, after rejection, with an allogeneic skin graft. Anti-non-Gal antibodies were detected after rejection of the GalT-KO skin, but there was no evidence for cross-reactivity against alloantigens, and the subsequent allograft was rejected in a time frame (day 10) consistent with a non-sensitized response.
Conclusions: Rejection of primary GalT-KO xenogeneic skin grafts leads to an anti-non-Gal humoral response with no evidence for cross-sensitization to alloantigens. These data suggest that GalT-KO skin grafts could provide an early first line clinical approach for severe burns that would not preclude subsequent use of allografts.
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