2011 - BSS 2011 Symposium
Oral Presentations 3
15.4 - Primary xenogeneic porcine alpha-1,3-galactosyltransferase knockout skin grafts do not cause sensitization of allogeneic humoral responses in a non-human primate model
Presenter: Alexander, Albritton, Boston, United States
Authors: Alexander Albritton1,3, Angelo Leto Barone1,2, Josef Kurtz1,3, Christopher Mallard1, David Sachs1, Curtis Cetrulo1,2
Primary xenogeneic porcine alpha-1,3-galactosyltransferase knockout skin grafts do not cause sensitization of allogeneic humoral responses in a non-human primate model
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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