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Investigation of red blood cells from α1,3‐galactosyltransferase‐knockout pigs for human blood transfusion
Author(s) -
Rouhani Foad J.,
Dor Frank J.M.F.,
Cooper David K.C.
Publication year - 2004
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2004.04002.x
Subject(s) - baboon , flow cytometry , antibody , epitope , microbiology and biotechnology , xenotransplantation , in vivo , biology , antigen , cytotoxicity , red blood cell , in vitro , immunoglobulin g , immunology , chemistry , transplantation , biochemistry , medicine , surgery , endocrinology
BACKGROUND: Pigs are a potential source of red blood cells (RBCs) for transfusion into humans, but the pre‐sence of galactose‐α1,3‐galactose (Gal) epitopes on their surface, against which humans have anti‐Gal, has been perceived as a major barrier. α1,3‐Galactosyltransferase gene‐knockout pigs, which do not express Gal epitopes on RBCs (Gal–/–), have recently become available. STUDY DESIGN AND 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. CONCLUSION: Pig RBCs are rapidly phagocytosed from the primate circulation by a mechanism not involving anti‐Gal.