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Antisense inhibition of pig α1,3galactosyl‐transferase leads to a reduction in expression of the major target for human natural antibodies on pig vascular endothelial cells
Author(s) -
Strahan Karen M.,
Preece Andrew F.,
Xu Yuanxin,
Gustafsson Kenth
Publication year - 1995
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1995.tb00082.x
Subject(s) - epitope , xenotransplantation , antibody , biology , antigen , microbiology and biotechnology , transplantation , monoclonal antibody , immunology , medicine
The expression of epitopes on pig cells for human natural antibodies (NAb) currently constitutes a major barrier to the use of pig organs and tissues in clinical transplantation. This is of particular significance to vascularized organs where the presence of carbohydrate antigens invariably leads to a hyperacute rejection when exposed to human blood or serum. It has been strongly suggested that the major antigen in this context consists of a terminal Galα1,3Galβ1,4GlcNAc trisaccharide. We have previously proposed that decreased expression of this epitope for human NAb may lead to elimination of hyperacute rejection. We have now used mRNA targeted antisense oligonucleotides to decrease the expression of the α1,3galactosyltransferase directing the terminal synthesis of this epitope on pig vascular endothelial cells. This mRNA antisense targeting leads to a decreased expression of the Galα1,3Galβ1,4GlcNAc structure as detected by epitope specific lectin. Moreover, a very similar reduction in mean fluorescence was seen when staining the same cells with human Galα1,3Galα1,4GlcNAc‐specific IgM NAb. We feel these findings constitute an important step in the process of providing conclusive evidence that reduction of or complete elimination of this epitope will overcome the hyperacute response in this species combination. In addition, such pig tissues may be less susceptible to further antibody rejection once the hyperacute phase has been overcome.