Ss. Lin et al., The role of anti-Gal alpha 1-3Gal antibodies in acute vascular rejection and accomodation of xenografts, TRANSPLANT, 70(12), 2000, pp. 1667-1674
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 wh
ether antibodies, binding to Gal alpha1-3Gal epitopes in porcine tissue, in
itiate this phenomenon.
Methods and results. Specific depletion of anti; Gal alpha1-3Gal antibodies
from the blood of baboons, using extracorporeal perfusion of separated pla
sma through columns of Sepharose beads covalently linked to the antigenic t
risaccharide, Gal alpha1-3Gal beta1-4GlcAc; averted the development of acut
e vascular rejection in porcine organs transgenic for human decay-accelerat
ing factor and CD59. More importantly, after immunodepletion was stopped an
d Gal alpha1-3Gal antibodies were allowed to return, these same organs cont
inued to function and remained pathologically normal and thus seemed to ach
ieve a state of accommodation.
Conclusion. These results demonstrate that antiGal alpha1-3Gal antibodies c
ause acute vascular rejection and suggest that depletion of these antibodie
s leads to accommodation of the donor cardiac xenograft and could supply an
important model for additional study.