ArticleXenotransplantation
Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock-out pigs.
Article in Xenotransplantation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Characterization of antibodies induced by immunization of mice with isoglobotrihexosylceramide (iGb3).Biochemistry and biophysics reports · 2024Article
- α-Gal antigen-deficient rabbits with GGTA1 gene disruption via CRISPR/Cas9.BMC genomic data · 2022Article
- Human immune reactivity of GGTA1/CMAH/A3GALT2 triple knockout Yucatan miniature pigs.Transgenic research · 2021Article
- The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation.Frontiers in immunology · 2020Review
- Gal epitope expression and immunological properties in iGb3S deficient mice.Scientific reports · 2018Article
- Recent advances in lung transplantation.F1000Research · 2018Review
- Article
- Optimized decellularization protocol including α-Gal epitope reduction for fabrication of an acellular porcine annulus fibrosus scaffold.Cell and tissue banking · 2017Article
- The Role of NK Cells in Pig-to-Human Xenotransplantation.Journal of immunology research · 2017Review
- Blood Groups in Infection and Host Susceptibility.Clinical microbiology reviews · 2015Review
- Comparative N-linked glycan analysis of wild-type and α1,3-galactosyltransferase gene knock-out pig fibroblasts using mass spectrometry approaches.Molecules and cells · 2015Article
- Double transgenic pigs with combined expression of human α1,2-fucosyltransferase and α-galactosidase designed to avoid hyperacute xenograft rejection.Archivum immunologiae et therapiae experimentalis · 2014Article
- Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Article
- Immunological challenges and therapies in xenotransplantation.Cold Spring Harbor perspectives in medicine · 2014Review
- Lung transplantation.F1000prime reports · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAnti-Galα1,3Galβ-R natural antibodies are responsible for hyperacute rejection in pig-to-primate xenotransplantation. Although the generation of pigs lacking the α1,3galactosyltransferase (GalT) has overcome hyperacute rejection, antibody-mediated rejection is still a problem. It is possible that other enzymes synthesize antigens similar to Galα1,3Gal epitopes that are recognized by xenoreactive antibodies. The glycosphingolipid isoglobotrihexosylceramide (iGb₃) represents such a candidate expressing an alternative Galα1,3Gal epitope. The present work determined whether the terminal Galα1,3Gal disaccharide is completely absent in Immerge pigs lacking the GalT using several different highly sensitive methods.
methodsThe expression of Galα1,3Gal was evaluated using a panel of antibodies and lectins by flow cytometry and fluorescent microscopy; GalT activity was detected by an enzymatic assay; and ion trap mass spectroscopy of neutral cellular membranes extracted from aortic endothelial was used for the detection of sugar structures. Finally, the presence of iGb₃ synthase mRNA was tested by RT-PCR in pig thymus, spleen, lymph node, kidney, lung, and liver tissue samples.
resultsAortic endothelial cells derived from GalT knockout pigs expressed neither Galα1,3Gal nor iGb₃ on their surface, and GalT enzymatic activity was also absent. Lectin staining showed an increase in the blood group H-type sugar structures present in GalT knockout cells as compared to wild-type pig aortic endothelial cells (PAEC). Mass spectroscopic analysis did not reveal Galα1,3Gal in membranes of GalT knockout PAEC; iGb₃ was also totally absent, whereas a fucosylated form of iGb₃ was detected at low levels in both pig aortic endothelial cell extracts. Isoglobotrihexosylceramide 3 synthase mRNA was expressed in all pig tissues tested whether derived from wild-type or GalT knockout animals.
conclusionsThese results confirm unequivocally the absence of terminal Galα1,3Gal disaccharides in GalT knockout endothelial cells. Future work will have to focus on other mechanisms responsible for xenograft rejection, in particular non-Galα1,3Gal antibodies and cellular responses.
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