Antibodies against MICA antigens and kidney-transplant rejection

N Engl J Med. 2007 Sep 27;357(13):1293-300. doi: 10.1056/NEJMoa067160.


Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Graft Rejection / immunology*
  • Graft Survival / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Testing
  • Humans
  • Immunoglobulin A / blood*
  • Kidney Transplantation / immunology*
  • Major Histocompatibility Complex
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Survival Analysis
  • Transplantation, Homologous


  • Histocompatibility Antigens Class I
  • Immunoglobulin A
  • MHC class I-related chain A