Studies on Glycolipid Antigens in Small Intestine and Pancreas from α1,3-Galactosyltransferase Knockout Miniature Swine

Diswall, Mette; Ångström, Jonas; Schuurman, Henk‐Jan; Dor, Frank J. M. F.; Rydberg, Lennart; Breimer, Michael E.

doi:10.1097/01.tp.0000287599.46165.15

Cited by 41 publications

(56 citation statements)

References 45 publications

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“…Detailed comparisons of glycolipids from GalT + and GalT-KO pig tissues (6, 7) find no evidence of the Gal antigen in GalT-KO samples but do detect increased amounts of lactosamine (Galβ4GlcNAc) the immediate precursor for both Gal and blood group H (O) antigen. Increased levels of P1 and x2 glycolipids have also been detected but these are also normal human glycans.…”

Section: Non-gal Pig Antigensmentioning

confidence: 98%

Recent investigations into pig antigen and anti-pig antibody expression

Byrne

McGregor

Breimer

2015

International Journal of Surgery

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Genetic engineering of donor pigs to eliminate expression of the dominant xenogeneic antigen galactose α1,3 galactose (Gal) has created a sea change in the immunobiology of xenograft rejection. Antibody mediated xenograft rejection of GGTA-1 α-galactosyltransferase (GTKO) deficient organs is now directed to a combination of non-Gal pig protein and carbohydrate antigens. Glycan analysis of GTKO tissues identified no new neo-antigens but detected high levels of N-acetylneuraminic acid (Neu5Gc) modified glycoproteins and glycolipids. Humans produce anti-Neu5Gc antibody and in very limited clinical studies sometimes show an induced anti-Neu5Gc antibody response after challenge with pig tissue. The pathogenicity of anti-Neu5Gc antibody in xenotransplantation is not clear however as non-human transplant models, critical for modelling anti-Gal immunity, do not produce anti-Neu5Gc antibody. Antibody induced after xenotransplantation in non-human primates is directed to an array of pig endothelial cells proteins and to a glycan produced by the pig B4GALNT2 gene. We anticipate that immune suppression will significantly affect the T-cell dependent and independent specificity of an induced antibody response and that donor pigs deficient in synthesis of multiple xenogeneic glycans will be important to future studies.

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Section: Non-gal Pig Antigensmentioning

confidence: 98%

Recent investigations into pig antigen and anti-pig antibody expression

Byrne

McGregor

Breimer

2015

International Journal of Surgery

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“…It is clearly present in neonatal and fetal pigs, but reduced expression has been observed in adult islets [28]. Thus, GTKO (1,3-galactosyltransferase gene-knockout) pigs are essential for using neonatal and fetal pig islets.…”

Section: Islet Source For Xenotransplantationmentioning

confidence: 98%

Current status of islet xenotransplantation

Park

Bottino

Hawthorne

2015

International Journal of Surgery

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“…Binding of human serum to glycosphingolipids on thin-layer chromatograms was performed as described (22). The human blood group AB serum pool was collected from 21 healthy blood donors and used at a dilution of 1:5.…”

Section: Methodsmentioning

confidence: 99%

Structural Complexity of Non-acid Glycosphingolipids in Human Embryonic Stem Cells Grown under Feeder-free Conditions

Barone

Benktander

Ångström

et al. 2013

Journal of Biological Chemistry

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Background: Carbohydrate epitopes are often used as markers for characterization of human embryonic stem cells (hESC). Results: Several glycosphingolipids not previously found in hESC were characterized. Conclusion: The glycosylation of hESC is more complex than previously thought. Significance: These findings will help to understand the immunogenicity of hESC and might impact future applications in regenerative medicine.

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Studies on Glycolipid Antigens in Small Intestine and Pancreas from α1,3-Galactosyltransferase Knockout Miniature Swine

Abstract: Knockout of porcine alpha1,3-galactosyltransferase gene results in elimination of Galalpha1,3Gal-terminated glycolipid compounds. GalT-KO genetic modification did not produce new compensatory glycolipid compounds reactive with human serum antibodies.

Cited by 41 publications

References 45 publications

Recent investigations into pig antigen and anti-pig antibody expression

Recent investigations into pig antigen and anti-pig antibody expression

Current status of islet xenotransplantation

Structural Complexity of Non-acid Glycosphingolipids in Human Embryonic Stem Cells Grown under Feeder-free Conditions

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