Antibodies against MICA Antigens and Kidney-Transplant Rejection

Abstract

Good HLA-A, HLA-B, and HLA-DR matches do not guarantee rejection-free renal transplantation. Some kidney transplants fail despite such matches, suggesting that other antigens might be targets for rejection. Major-histocompatibility-complex (MHC) class I-related chain A (MICA) antigens are polymorphic and can elicit antibody production. We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts. Pretransplantation serum samples from 1910 recipients of kidney transplants from deceased donors were tested for anti-MICA antibodies with an assay in which single MICA antigens were attached to polystyrene microspheres. Antibodies against MICA alleles were detected in 217 of the 1910 patients (11.4%). The presence of MICA antibodies was associated with renal-allograft rejection. The mean (+/-SE) 1-year graft-survival rate was 88.3+/-2.2% among recipients with anti-MICA antibodies as compared with 93.0+/-0.6% among recipients without anti-MICA antibodies (P=0.01). Among recipients of first kidney transplants, the survival rate was even lower among MICA antibody-positive patients (87.8+/-2.4%) than among MICA antibody-negative recipients (93.5+/-0.6%, P=0.005). In addition, the association of MICA sensitization with reduced graft survival was more evident in kidney-transplant recipients with good HLA matching: among 326 recipients who received well-matched kidneys (0 or 1 HLA-A plus HLA-B plus HLA-DR mismatch), sensitization against MICA was associated with poorer allograft survival (83.2+/-5.8% among those with anti-MICA antibodies vs. 95.1+/-1.3% among those without such antibodies, P=0.002). Presensitization of kidney-transplant recipients against MICA antigens is associated with an increased frequency of graft loss and might contribute to allograft loss among recipients who are well matched for HLA.