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American Journal of Transplantation
Article . 2014 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Authors: Burlak, C.; Paris, L. L.; Lutz, A. J.; Sidner, R. A.; Estrada, J.; Li, P.; Tector, M.; +1 Authors

Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs

Abstract

Xenotransplantation using genetically modified pig organs could solve the donor organ shortage problem. Two inactivated genes that make humans unique from pigs are GGTA1 and CMAH, the products of which produce the carbohydrate epitopes, aGal and Neu5Gc that attract preformed human antibody. When the GGTA1 and CMAH genes were deleted in pigs, human antibody binding was reduced in preliminary analysis. We analyzed the binding of human IgM and IgG from 121 healthy human serum samples for binding to GGTA1 KO and GGTA1/CMAH KO peripheral blood mononuclear cells (PBMCs). We analyzed a sub population for reactivity toward genetically modified pig PBMCs as compared to chimpanzee and human PBMCs. Deletion of the GGTA1 and CMAH genes in pigs improved the crossmatch results beyond those observed with chimpanzees. Sorting the 121 human samples tested against the GGTA1/CMAH KO pig PBMCs did not reveal a distinguishing feature such as blood group, age or gender. Modification of genes to make pig carbohydrates more similar to humans has improved the crossmatch with human serum significantly.

Country
United States
Keywords

Adult, Graft Rejection, Male, Adolescent, Pan troglodytes, Carbohydrates, 1600-6143, Middle Aged, Galactosyltransferases, Antibodies, Animals, Genetically Modified, Epitopes, Immunoglobulin M, Immunoglobulin G, Leukocytes, Mononuclear, Animals, Humans, Female, Gene Deletion, Aged, Protein Binding

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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
85
Top 10%
Top 10%
Top 10%
hybrid