Hyporesponsiveness against donor’s ABO antigens of renal grafts after ABO-incompatible kidney transplantation

Background ABO antigens expressed on the red blood cells (RBCs) are not identical to those expressed on the renal endothelial cells. The isohemagglutinin assay employing the RBCs is the gold standard for evaluating anti-ABO antibody (Ab) levels. However, it remains unclear whether the anti-ABO Abs detected by the isohemagglutinin assay after ABO-incompatible (ABOi) kidney transplantations (KTx) that are not associated with antibody-mediated rejection can bind to renal graft endothelial cells. Methods Ninety plasma samples were collected from patients with stable graft function after ABO-compatible (ABOc) or ABOi KTx. Anti-ABO Ab titers were examined by both the isohemagglutinin assay and the CD31-ABO microarray, which was developed as a mimic of the ABO antigens expressed on the renal endothelial cells. Results The antibody titers detected by the isohemagglutinin assay and the CD31-ABO microarray after the ABOc KTx relatively correlated with each other. However, the CD31-ABO microarray results showed low antibody levels against donor blood group antigens after ABOi KTx and did not correlate with the isohemagglutinin assay. In contrast, the antibody levels against non-donor blood group antigens after ABOi KTx were comparable to those after the ABOc KTx. Fourteen patients received graft biopsies, and no antibody-mediated rejection was observed in ABOi KTx recipients, except for two patients who had anti-donor-HLA Abs. Conclusion The present study suggested that the anti-ABO Abs detected by the isohemagglutinin assay after ABOi KTx with stable graft function were hyporeactive to the ABO antigen of graft renal endothelial cells.