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Demonstration of the functional importance of the Gal epitope in an ex vivo model of xenotransplantation
Author(s) -
Iange M.J.,
Tearle R.G.,
Aminian L.,
Romanella M.,
Adam W.R.,
Pearse M.J.,
D'Apice A.J.F.
Publication year - 1997
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.1399-3089.1997.tb00160.x
Subject(s) - epitope , xenotransplantation , antibody , knockout mouse , galactosyltransferase , ex vivo , antigen , in vivo , immunology , transplantation , biology , chemistry , microbiology and biotechnology , medicine , biochemistry , gene , enzyme
The galactose a 1‐3 galactose terminal disaccharide (Gal epitope) has been identified as the major porcine xenoantigen recognised by xenoantibody in human plasma. Elimination or suppression of the epitope or antibody will be a major factor in overcoming hyperacute rejection. Inhibition of the antibody by depletion or elimination of the epitope by gene knockout may reveal the importance of other xenoantibodies, and in addition elimination of the epitope may unmask or produce other xenoantibody combinations. This study aims to determine the relative importance of anti‐Gal antibody and Gal epitope elimination in a functional model of xenotransplantation, ex vivo perfusion of mouse hearts with human plasma on a Langendorff apparatus. Perfusion of mouse hearts with human plasma depleted of anti‐Gal antibody demonstrates a protective effect compared to hearts perfused with undepleted plasma with prolongation of survival time from 24.1 to 44.5 min. Similarly, elimination of the epitope is also protective. Hearts from Gal knockout mice, which were generated by gene targeting of the al,3 galactosyltransferase gene, and hearts from appropriate control mice were perfused with human plasma. Gal knockout mice hearts demonstrated an increase in survival time from 10.2 to 33.8 min compared to control hearts. This was accompanied by a decrease in C3c and IgM, but little change in IgG deposition. The protective effect is incomplete, probably due to the effect of antibodies against non‐Gal xenoantigens. There was no functional evidence for generation of neo‐antigens in the Gal KO mice that were I recognised by naturally occurring human xenoantibodies.