BACKGROUND: This study investigates anti-nonGal antibodies (Abs) in baboons after alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation (Tx). METHODS: Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. RESULTS: Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). CONCLUSIONS: Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer.
BACKGROUND: This study investigates anti-nonGal antibodies (Abs) in baboons after alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation (Tx). METHODS: Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. RESULTS: Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). CONCLUSIONS: Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer.
Authors: M M Mohiuddin; P C Corcoran; A K Singh; A Azimzadeh; R F Hoyt; M L Thomas; M A Eckhaus; C Seavey; D Ayares; R N Pierson; K A Horvath Journal: Am J Transplant Date: 2011-11-09 Impact factor: 8.086
Authors: Davide Ricci; Henry D Tazelaar; Naoto Miyagi; Vinay P Rao; Rachel A Pedersen; Walter K Kremers; Guerard W Byrne; Christopher G A McGregor Journal: J Heart Lung Transplant Date: 2007-10 Impact factor: 10.247
Authors: Guerard W Byrne; Paul G Stalboerger; Eduardo Davila; Carrie J Heppelmann; Mozammel H Gazi; Hugh C J McGregor; Peter T LaBreche; William R Davies; Vinay P Rao; Keiji Oi; Henry D Tazelaar; John S Logan; Christopher G A McGregor Journal: Xenotransplantation Date: 2008 Jul-Aug Impact factor: 3.907
Authors: Karen Kim; Christian Schuetz; Nahel Elias; Gregory R Veillette; Isaac Wamala; Manish Varma; R Neal Smith; Simon C Robson; A Benedict Cosimi; David H Sachs; Martin Hertl Journal: Xenotransplantation Date: 2012 Jul-Aug Impact factor: 3.907
Authors: Agnes M Azimzadeh; Guerard W Byrne; Mohamed Ezzelarab; Emily Welty; Gheorghe Braileanu; Xiangfei Cheng; Simon C Robson; Christopher G A McGregor; David K C Cooper; Richard N Pierson Journal: Xenotransplantation Date: 2014-09-01 Impact factor: 3.907
Authors: Richard N Pierson; Anthony Dorling; David Ayares; Michael A Rees; Jörg D Seebach; Jay A Fishman; Bernhard J Hering; David K C Cooper Journal: Xenotransplantation Date: 2009 Sep-Oct Impact factor: 3.907