The role of anti-Galalpha1-3Gal antibodies in acute vascular rejection and accommodation of xenografts.
BACKGROUND
A major impediment to the transplanting of porcine organs into humans is the susceptibility of porcine organs to acute vascular rejection, which can destroy a vascularized xenograft over a period of hours to days. Acute vascular rejection of porcine-to-primate xenografts is thought to be triggered by binding of xenoreactive antibodies to the graft. We tested whether antibodies, binding to Galalpha1-3Gal epitopes in porcine tissue, initiate this phenomenon.


RESULTS
Specific depletion of anti-Galalpha1-3Gal antibodies from the blood of baboons, using extracorporeal perfusion of separated plasma through columns of Sepharose beads covalently linked to the antigenic trisaccharide, Galalpha1-3Galbeta1-4GlcAc, averted the development of acute vascular rejection in porcine organs transgenic for human decay-accelerating factor and CD59. More importantly, after immunodepletion was stopped and Gala1-3Gal antibodies were allowed to return, these same organs continued to function and remained pathologically normal and thus seemed to achieve a state of accommodation.


CONCLUSIONS
These results demonstrate that anti-Galalpha1-3Gal antibodies cause acute vascular rejection and suggest that depletion of these antibodies leads to accommodation of the donor cardiac xenograft and could supply an important model for additional study.
Lin
S S
SS
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Hanaway
M J
MJ
Gonzalez-Stawinski
G V
GV
Lau
C L
CL
Parker
W
W
Davis
R D
RD
Byrne
G W
GW
Diamond
L E
LE
Logan
J S
JS
Platt
J L
JL
D000208:Acute Disease; D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000276:immunology* / Q000302:isolation & purification; D018958:CD55 Antigens / Q000235:genetics; D018957:CD59 Antigens / Q000235:genetics; D004187:Disaccharides / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006801:Humans; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D018958:CD55 Antigens; D018957:CD59 Antigens; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose