Antigen expression in xenotransplantation: How low must it go?

Background. Acute vascular rejection (AVR) is an important immunological ba rrier to xenotransplantation. Thought to be initiated by xenoreactive antib odies, acute vascular rejection might, in principle, be avoided by engineer ing animals to express low levels of antigen. The extent to which antigen e xpression would have to be decreased to achieve such a goal is unknown. Methods. We estimated the decrease in expression of a xenogeneic antigen, G al alpha1-3Gal, which might be needed to avert acute vascular rejection of xenotransplants based on the decrease in antibody binding to endothelium th at would prevent tissue damage, Results. The level of decrease needed in Gal alpha1-3Gal expression needed to avoid acute vascular rejection was estimated to exceed 96% of baseline. The extent of the decrease needed reflected, in part, a substantial "excess " of Gal alpha1-3Gal on porcine endothelial cell surfaces. Conclusions. Although the change in antigen expression required to avoid ac ute vascular rejection might be conditioned by various factors, the very la rge magnitude of this change necessitates application of highly efficient a pproaches to antigen modification.