ABO-incompatible transplantation: Accommodation by upregulation of protective genes - A hypothesis

ABO-incompatible kidney and liver transplants can be performed successfully by depleting anti-A or anti-B isoagglutinins pretransplant and by suppressing their development posttransplant. With these protocols, humoral rejection can be avoided. Recovery of isohemagglutinin antibody levels without humoral rejection suggests accommodation, the ability of an organ allograft to survive in the presence of anti-graft antibodies and complement, may be the protective mechanism preventing late antibody-mediated rejection. This may be related to the ability of endothelial cells, the target of antibody-mediated rejection, to upregulate protective genes, including those encoding heme oxygenase-1 (HO-1) that then block the proinflammatory response of the endothelial cells and thereby rejection. Induced expression of HO-1 in the endothelial cells of the graft before transplantation may prevent apoptosis of those cells after transplantation, and prevent the generation of endothelial cell-based inflammation that leads to rejection. Experimental and clinical studies in ABO-incompatible models will be required to examine this hypothesis, and determine whether carbon monoxide (CO) might be able to modulate antibody-mediated rejection after ABO-incompatible transplantation.