BACKGROUND: As pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) are available, primate antibodies to pig non-Gal antigens can be studied. METHODS: Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs by flow cytometry. Complement-dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT-KO pig heart, one not immunosuppressed and one that received only cobra venom factor. RESULTS: IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT-KO PBMC, respectively (WT vs. GT-KO, P<0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P<0.05). In the two baboons exposed to GT-KO hearts, anti-non-Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT-KO PBMC. CONCLUSIONS: Two-thirds of baboon sera demonstrated cytotoxicity to GT-KO PBMC. After GT-KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.
BACKGROUND: As pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) are available, primate antibodies to pig non-Gal antigens can be studied. METHODS: Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs by flow cytometry. Complement-dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT-KO pig heart, one not immunosuppressed and one that received only cobra venom factor. RESULTS: IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT-KO PBMC, respectively (WT vs. GT-KO, P<0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P<0.05). In the two baboons exposed to GT-KO hearts, anti-non-Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT-KO PBMC. CONCLUSIONS: Two-thirds of baboon sera demonstrated cytotoxicity to GT-KO PBMC. After GT-KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.
Authors: Hidetaka Hara; Andrew Bentall; Cassandra Long; Jason Fang; Oleg Andreyev; John Lunz; Mohamed Ezzelarab; Kareem M Abu-Elmagd; Ron Shapiro; David Ayares; Mark Stegall; David K C Cooper Journal: Xenotransplantation Date: 2013-09-03 Impact factor: 3.907
Authors: P Thompson; I R Badell; M Lowe; J Cano; M Song; F Leopardi; J Avila; R Ruhil; E Strobert; G Korbutt; G Rayat; R Rajotte; N Iwakoshi; C P Larsen; A D Kirk Journal: Am J Transplant Date: 2011-08-29 Impact factor: 8.086
Authors: Hayato Iwase; Burcin Ekser; Vikas Satyananda; Jay Bhama; Hidetaka Hara; Mohamed Ezzelarab; Edwin Klein; Robert Wagner; Cassandra Long; Jnanesh Thacker; Jiang Li; Hao Zhou; Maolin Jiang; Santosh Nagaraju; Huidong Zhou; Massimiliano Veroux; Pietro Bajona; Martin Wijkstrom; Yi Wang; Carol Phelps; Nikolai Klymiuk; Eckhard Wolf; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2015-04-03 Impact factor: 3.907
Authors: Burcin Ekser; Christopher Burlak; Joshua P Waldman; Andrew J Lutz; Leela L Paris; Massimiliano Veroux; Simon C Robson; Michael A Rees; David Ayares; Bruno Gridelli; A Joseph Tector; David Kc Cooper Journal: Expert Rev Clin Immunol Date: 2012-09 Impact factor: 4.473