ArticleXenotransplantation2021
Histopathology of pig kidney grafts with/without expression of the carbohydrate Neu5Gc in immunosuppressed baboons.
Article in Xenotransplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Graft rejection in paediatric congenital heart disease.Translational pediatrics · 2023Review
- Transitioning of renal transplant pathology from allograft to xenograft and tissue engineering pathology: Are we prepared?World journal of transplantation · 2023Review
- Milestones on the path to clinical pig organ xenotransplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Review
- Cardiac xenotransplantation: from concept to clinic.Cardiovascular research · 2023Review
- Developments in kidney xenotransplantation.Frontiers in immunology · 2023Review
- Immune disguise: the mechanisms of Neu5Gc inducing autoimmune and transplant rejection.Genes and immunity · 2022Review
- The first clinical pig heart transplant: Was IVIg or pig cytomegalovirus detrimental to the outcome?Xenotransplantation · 2022Review
- The 2021 IXA Keith Reemtsma Lecture: Moving xenotransplantation to the clinic.Xenotransplantation · 2022Review
- Current Topics of Relevance to the Xenotransplantation of Free Pig Islets.Frontiers in immunology · 2022Review
- In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.XenotransplantationArticle
- Antibody-mediated rejection in xenotransplantation: Can it be prevented or reversed?XenotransplantationReview
- Early Experimental Report of the First 8-Gene-Edited Pig-to-Rhesus Macaque Cardiac Xenotransplantation in China.XenotransplantationArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionPigs deficient in three glycosyltransferase enzymes (triple-knockout [TKO] pigs, that is, not expressing the three known carbohydrate xenoantigens) and expressing 'protective' human transgenes are considered a likely source of organs for transplantation into human recipients. Some human sera have no or minimal natural antibody binding to red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) from TKO pigs. However, all Old World monkeys exhibit natural antibody binding to TKO pig cells. The xenoantigen targets of Old World monkey natural antibodies are postulated to be carbohydrate moieties exposed when the expression of the carbohydrate N-glycolylneuraminic acid (Neu5Gc) is deleted. The aim of this study was to compare the survival in baboons and histopathology of renal grafts from pigs that either (a) expressed Neu5Gc (GTKO pigs; Group 1) or (b) did not express Neu5Gc (GTKO/CMAHKO [DKO] or TKO pigs; Group 2).
methodsLife-supporting renal transplants were carried out using GTKO (n = 5) or DKO/TKO (n = 5) pig kidneys under an anti-CD40mAb-based immunosuppressive regimen.
resultsGroup 1 baboons survived longer than Group 2 baboons (median 237 vs. 35 days; mean 196 vs. 57 days; p < 0.07) and exhibited histopathological features of antibody-mediated rejection in only two kidneys. Group 2 exhibited histopathological features of antibody-mediated rejection in all five grafts, with IgM and IgG binding to renal interstitial arteries and peritubular capillaries. Rejection-free survival was significantly longer in Group 1 (p < 0.05).
conclusionsThe absence of expression of Neu5Gc on pig kidney grafts is associated with increased binding of baboon antibodies to pig endothelium and reduced graft survival.
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