Human anti-α-fucose antibodies are xenoreactive toward GGTA1/CMAH knockout pigs

Xenotransplantation. 2020 Nov;27(6):e12629. doi: 10.1111/xen.12629. Epub 2020 Jul 22.


Progress has been made in overcoming antibody-mediated rejection of porcine xenografts by deleting pig genes that produce unique carbohydrate epitopes. Pigs deficient in galactose α-1,3 galactose (gene modified: GGTA1) and neu5Gc (gene modified: CMAH) have reduced levels of human antibody binding. Previously we identified α-fucose as a glycan that was expressed in high levels on cells of GGTA1/CMAH KO pigs. To validate the α-fucose phenotype observed previously we compared lectin affinity toward human and pig serum glycoproteins by dot blot analysis and confocal microscopy. Human anti-fucose antibody isolated by affinity chromatography was tested for specificity to L-fucose by custom macroarray. The affinity and cytotoxicity of the isolated human anti-fucose antibody toward human and GGTA1/CMAH KO pig PBMCs was determined by flow cytometry. Dot blot and confocal analysis support out previous findings that α-fucose is more highly expressed in pigs than humans. Pig kidney glomeruli and tubules contain abundant α-fucose and may represent focal sites for anti-α-fucose antibody binding. The Isolated human anti-fucose IgA, IgG and IgM bound to GGTA1/CMAH KO pig PBMC and were cytotoxic. Interestingly, the isolated human IgG cross reacted with the methyl pentose, L-rhamnose. Human anti-fucose antibody bound and was cytotoxic to GGTA1/CMAH KO pig peripheral blood monocytes. We have shown that α-fucose is an abundant target for cytotoxic human antibody in the organs of genetically modified pigs important to xenotransplantation.

Keywords: N-linked oligosaccharide; Xenoantigens; antibody-mediated rejection; fucose; fucosyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Antigens, Heterophile / immunology*
  • Fucose* / immunology
  • Galactosyltransferases
  • Gene Knockout Techniques
  • Humans
  • Leukocytes, Mononuclear
  • Mixed Function Oxygenases
  • Swine
  • Transplantation, Heterologous*


  • Antigens, Heterophile
  • Fucose
  • Mixed Function Oxygenases
  • CMPacetylneuraminate monooxygenase
  • Galactosyltransferases
  • alpha-1,3-galactosyltransferase 1, porcine