Cardiac allotransplantation across the ABO-blood group barrier by the neutralization of preformed antibodies: the baboon as a model for the human.
The baboon, like the human, expresses A and/or B blood group antigens on its tissues. Anti-A and anti-B antibodies are directed against these antigens, the epitopes of which are carbohydrate structures. Portions of these carbohydrates have been synthesized (trisaccharides A and B, respectively). When infused intravenously, the synthetic trisaccharides form a complex with the specific antibodies and neutralize their activity preventing them from binding to the antigen targets on a transplanted organ. In nonimmunosuppressed, hyperimmunized baboons, the continuous intravenous infusion of the specific trisaccharide alone (for 6 days) inhibited rejection of ABO-incompatible cardiac allografts, extending survival from a mean of 19 min (n = 3) to 8 days (n = 2), at which time the grafts failed from cellular (not vascular) rejection. The combination of long-term pharmacologic immunosuppression plus trisaccharide infusion (for periods of 8 to 19 days) extended survival to a mean of > 28 days (n = 4) with one heart functioning > 52 days. Accommodation clearly occurred in three of the four cases. This form of therapy may permit cadaveric organ allotransplantation across the ABO blood-group barrier in the human.
Oklahoma Transplantation Institute, Oklahoma City.
Y
Y
Ye
M
M
Niekrasz
M
M
Kehoe
L L
LL
Rolf
M
M
Martin
J
J
Baker
S
S
Kosanke
E
E
Romano
N
N
Zuhdi
D K
DK
Cooper
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D000936:Antigen-Antibody Complex; D001787:Blood Group Incompatibility / Q000276:immunology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000379:methods*; D007114:Immunization; D007165:Immunosuppression Therapy; D009500:Neutralization Tests; D010215:Papio; D014184:Transplantation, Homologous / Q000379:methods; D014312:Trisaccharides / Q000008:administration & dosage / Q000276:immunology
D000017:ABO Blood-Group System; D000936:Antigen-Antibody Complex; D014312:Trisaccharides