1. Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans
- Author
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Zuhaib Ibrahim, Xiaocheng Zhu, Michel Awwad, Yih Jyh Lin, Hidetaka Hara, David Ayares, Pleunie P. M. Rood, David K. C. Cooper, Mohamed Ezzelarab, Adriana Zeevi, Suyapa Ball, and Jamie Busch
- Subjects
Cytotoxicity, Immunologic ,Graft Rejection ,Isoantigens ,Swine ,Xenotransplantation ,medicine.medical_treatment ,Immunology ,Disaccharides ,Peripheral blood mononuclear cell ,Immunoglobulin G ,Antigen ,Transplantation Immunology ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Transplantation ,biology ,Immune Sera ,Panel reactive antibody ,Cytotoxicity Tests, Immunologic ,Molecular biology ,Immunoglobulin M ,Leukocytes, Mononuclear ,biology.protein ,Antibody - Abstract
Background: The availability of pigs homozygous for α1,3-galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Galα1,3Gal (Gal), termed non-Gal antigens. Methods: Sera from 27 healthy humans and 31 patients awaiting renal allotransplantation, who were either unsensitized [panel reactive antibodies (PRA) 70%), were tested by flow cytometry for binding of immunoglobulin M (IgM) and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs. Complement-dependent cytotoxicity to WT and GT-KO PBMC was also measured. Results: IgM and IgG from all 27 (100%) healthy human sera bound to WT PBMC, while 78% and 63% of these sera had IgM and IgG that bound to GT-KO PBMC, respectively. Mean binding to WT PBMC was significantly greater than GT-KO PBMC. Whereas 100% of sera were cytotoxic to WT PBMC, only 61% were cytotoxic to GT-KO PBMC, and the extent of lysis was significantly less. Neither mean binding of IgM and IgG nor cytotoxicity of unsensitized and allosensitized sera to WT and GT-KO PBMC was significantly different to that of healthy sera. Conclusions: More than half of the healthy humans tested had cytotoxic antibodies to GT-KO PBMC, but allosensitized patients will be at no greater risk of rejecting a pig xenograft by a humoral mechanism.
- Published
- 2006