Elicited non-anti-alphaGAL antibodies may cause acute humoral rejection of hDAF pig organs transplanted in baboons.
The combination of immunosuppression and GAS 914, a polylysine containing alphaGal trisaccharide type 2 (TRI 2), has been associated with the prevention of acute humoral xenograft rejection (AHXR) in human decay accelerating factor (hDAF) pig-to-baboon xenotransplants. The aim of this study was to investigate the role of immunosuppression and GAS 914 to neutralize xenoantibodies before and after xenotransplantation. Eight baboons underwent heteropic heart xenotransplantation with hDAF transgenic pig organs, receiving GAS 914 before and after transplantation. Six baboons (Group A) were treated with an immunosuppression protocol that included cyclophosphamide (CyP), Neoral, ERL, and steroids. The other 2 baboons (Group B) were treated with the same immunosuppression but with a 50% reduction in the doses of CyP. No xenograft from Group A underwent acute humoral xenograft (median survival, 27 days), whereas the 2 in Group B experienced rejection (median survival, 6 days). GAS 914 depleted both immunoglobulin (Ig)M and IgG anti-alphaGAL disaccharide (DI), trisaccharide type 2 (TRI 2), and trisaccharide type 6 (TRI 6), before and after transplantation in Groups A and B. However, cytotoxic antibodies with other anti-pig specificities were elicited by the xenografts in Group B leading to AHXR.
Doménech
N
N
Research Unit, CHU Juan Canalejo, La Coruña, Spain.
Diaz
T
T
Moscoso
I
I
López-Peláez
E
E
Centeno
A
A
Máñez
R
R
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000276:immunology*; D018958:CD55 Antigens / Q000235:genetics* / Q000276:immunology; D004187:Disaccharides / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D010215:Papio; D013552:Swine; D014312:Trisaccharides / Q000627:therapeutic use
D000910:Antibodies, Heterophile; D018958:CD55 Antigens; D004187:Disaccharides; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; C055075:galactosyl-(1-3)galactose