| Autor: |
Littera, Roberto, Mocci, Stefano, Argiolas, Davide, Littarru, Letizia, Lai, Sara, Melis, Maurizio, Sanna, Celeste, Mereu, Caterina, Lorrai, Michela, Mascia, Alessia, Angioi, Andrea, Mascia, Giacomo, Matta, Valeria, Lepori, Nicola, Floris, Matteo, Manieli, Cristina, Bianco, Paola, Onnis, Daniela, Rassu, Stefania, Deidda, Silvia |
| Zdroj: |
Frontiers in Immunology; 2024, p1-20, 20p |
| Abstrakt: |
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 (X2 = 6.95; Log-rank=0.031). Notably, the rs1049174[GG] genotype contributes to a significantly increased risk of antibody-mediated rejection (X2 = 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 (X2 = 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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