Investigation of red blood cells from alpha1,3-galactosyltransferase-knockout pigs for human blood transfusion.
BACKGROUND
Pigs are a potential source of red blood cells (RBCs) for transfusion into humans, but the presence of galactose-alpha1,3-galactose (Gal) epitopes on their surface, against which humans have anti-Gal, has been perceived as a major barrier. alpha1,3-Galactosyltransferase gene-knockout pigs, which do not express Gal epitopes on RBCs (Gal-/-), have recently become available.


METHODS
In vitro, RBCs from Gal-/- pigs were exposed to sera from naïve humans or baboons or from baboons previously sensitized to pig antigens; immunoglobulin binding was measured by flow cytometry, and cytotoxicity, by a hemolytic assay. In vivo, relatively small numbers of Gal-/- RBCs were transfused into two nonsensitized untreated baboons. The survival of pig RBCs was detected by flow cytometry.


RESULTS
In vitro, binding of immunoglobulin (Ig) M from naïve human or baboon sera was detected to Gal-/- RBCs but was significantly less than to Gal+/+ RBCs; IgG binding to Gal-/- RBCs was absent or minimal. Sera had minimal cytotoxicity to Gal-/- RBCs compared to Gal+/+ RBCs. Sensitized baboon sera demonstrated much higher IgG binding to Gal-/- RBCs and increased cytotoxicity, but again these were less than to Gal+/+ RBCs. In vivo, the transfusion of relatively small volumes of Gal-/- RBCs was followed by detection of the cells in the baboon's blood for only 5 minutes.


CONCLUSIONS
Pig RBCs are rapidly phagocytosed from the primate circulation by a mechanism not involving anti-Gal.
Rouhani
Foad J
FJ
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.
Dor
Frank J M F
FJ
Cooper
David K C
DK
D000818:Animals; D030801:Animals, Genetically Modified; D004187:Disaccharides / Q000276:immunology*; D017707:Erythrocyte Transfusion; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000235:genetics*; D006461:Hemolysis; D006801:Humans; D010215:Papio; D013552:Swine
D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase