Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs

C. Burlak, L. L. Paris, A. J. Lutz, R. A. Sidner, J. Estrada, P. Li, M. Tector, A. J. Tector

Research output: Contribution to journalArticle

48 Scopus citations

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. Crossmatch analysis of human antibody binding to cells from pigs genetically modified for xenotransplantation is similar to allogeneic cells, lower than chimpanzee cells, and unaffected by age, gender, or blood type.

Original languageEnglish (US)
Pages (from-to)1895-1900
Number of pages6
JournalAmerican Journal of Transplantation
Volume14
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • Antibody-mediated rejection
  • crossmatch
  • genetically modified pigs
  • xenotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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    Burlak, C., Paris, L. L., Lutz, A. J., Sidner, R. A., Estrada, J., Li, P., Tector, M., & Tector, A. J. (2014). Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs. American Journal of Transplantation, 14(8), 1895-1900. https://doi.org/10.1111/ajt.12744