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

Am J Transplant. 2014 Aug;14(8):1895-900. doi: 10.1111/ajt.12744. Epub 2014 Jun 6.

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.

Keywords: Antibody-mediated rejection; crossmatch; genetically modified pigs; xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Animals, Genetically Modified
  • Antibodies / chemistry*
  • Carbohydrates / chemistry
  • Epitopes / chemistry
  • Female
  • Galactosyltransferases / genetics*
  • Gene Deletion
  • Graft Rejection
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / chemistry
  • Leukocytes, Mononuclear / cytology
  • Male
  • Middle Aged
  • Pan troglodytes
  • Protein Binding
  • Swine
  • Transplantation, Heterologous*

Substances

  • Antibodies
  • Carbohydrates
  • Epitopes
  • Immunoglobulin G
  • Immunoglobulin M
  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine