MICA and NKG2D gene polymorphisms influence graft survival, and response to therapy in kidney transplantation.

Background: Antibody-mediated rejection is a significant cause of kidney transplant failure. Recent studies have shown that the MHC class I MICA gene influences the transplantation outcome. However, the role of the primary MICA receptor, NKG2D, has yet to be explored.
Aim: We aimed to investigate the correlation between recipient/donor MICA allele matching and NKG2D genotype with the risk of antibody-mediated rejection and their potential clinical effects and implications for organ maintenance therapy.
Methods: Of the 524 patients who underwent transplantation, 387 were eligible for the study. Complete MICA allele and two functional polymorphisms of NKG2D ( rs1049174C>G and rs2255336G>A ) were analyzed in 148 transplanted patients and 146 controls.
Results: Increased recipient/donor MICA allele mismatches correlate with an elevated risk of antibody-mediated rejection (X ² = 6.95; Log-rank=0.031). Notably, the rs1049174[GG] genotype contributes to a significantly increased risk of antibody-mediated rejection (X ² = 13.44; Log-rank=0.001 and X ² = 0.34; Log-rank=0.84). The combined effect of two MICA allele mismatches and rs1049174[GG] genotype shows the highest risk (X ² = 23.21; Log-rank<0.001). Most importantly, patients with rs1049174[GG] and rs2255336[ AA ] genotypes may respond less to mTOR inhibitor immunosuppressive therapy than Calcineurin inhibitors ( rs1049174[GG]; P=0.035; and rs2255336[AA] ; P=0.002).
Conclusion: Recipient/donor MICA allele mismatches and specific NKG2D variants, as well as their combinations, influence kidney transplant outcomes, providing insights for personalized treatment and enhancing graft survival.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Littera, Mocci, Argiolas, Littarru, Lai, Melis, Sanna, Mereu, Lorrai, Mascia, Angioi, Mascia, Matta, Lepori, Floris, Manieli, Bianco, Onnis, Rassu, Deidda, Carta, Giuressi, Perra, Chessa, Giglio and Pani.)