The identification of histocompatibility loci, beyond human leukocyte antigen (HLA), and of antibodies directed against non-HLA antigens that contribute to kidney allograft rejection may aid in donor–recipient matching and improve outcomes for transplant recipients. New research in a large cohort of recipients of kidney transplants has now identified MICA — which encodes a non-conventional MHC class I molecule — as a histocompatibility locus and demonstrates that anti-MICA donor-specific antibodies (DSAs) are strongly associated with antibody-mediated rejection (ABMR). “Although previous studies performed on smaller cohorts and focusing mainly on anti-MICA immunization suggested a potential role of MICA in transplantation, we believe our study now formally identifies MICA as a new transplantation antigen in the kidney allograft,” explains researcher Seiamak Bahram. “In our cohort, the MICA effect was even higher than that of the other classical class I HLA genes, which was quite unexpected.”
Over a median follow-up of 6.3 years after transplantation, recipients of transplants from MICA genotype-matched donors had significantly better graft survival than those of transplants from MICA-mismatched donors (96% and 88% graft survival for MICA-matched and mismatched patients, respectively, at 5 years after transplantation). MICA mismatch was an independent risk factor for graft loss (HR 2.12, 95% CI 1.45–3.11; P < 0.001). In a subset of transplant recipients, the presence of pre-transplantation and post-transplantation anti-MICA DSAs was also associated with an increased incidence of acute rejection, particularly ABMR. “This effect was more important when these antibodies developed de novo, after transplantation, and was synergetic with the effect of anti-HLA DSAs,” says Bahram. In an independent cohort of 168 patients who had experienced an episode of ABMR, the presence of anti-MICA DSAs was associated with reduced graft survival (HR 1.71, 95% CI 1.02–2.86; P = 0.041).
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