{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:27Z","timestamp":1787026527202,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014810","name":"Fondazione di Sardegna","doi-asserted-by":"publisher","award":["40974"],"award-info":[{"award-number":["40974"]}],"id":[{"id":"10.13039\/100014810","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n Antibody-mediated rejection is a significant cause of kidney transplant failure. Recent studies have shown that the MHC class I\n MICA<\/jats:italic>\n gene influences the transplantation outcome. However, the role of the primary\n MICA<\/jats:italic>\n receptor, NKG2D, has yet to be explored.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n We aimed to investigate the correlation between recipient\/donor\n MICA<\/jats:italic>\n allele matching and\n NKG2D<\/jats:italic>\n genotype with the risk of antibody-mediated rejection and their potential clinical effects and implications for organ maintenance therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Of the 524 patients who underwent transplantation, 387 were eligible for the study. Complete\n MICA<\/jats:italic>\n allele and two functional polymorphisms of\n NKG2D<\/jats:italic>\n (\n rs1049174C&gt;G<\/jats:italic>\n and\n rs2255336G&gt;A<\/jats:italic>\n ) were analyzed in 148 transplanted patients and 146 controls.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Increased recipient\/donor\n MICA<\/jats:italic>\n allele mismatches correlate with an elevated risk of antibody-mediated rejection (X\n 2<\/jats:sup>\n = 6.95; Log-rank=0.031). Notably, the\n rs1049174[GG]<\/jats:italic>\n genotype contributes to a significantly increased risk of antibody-mediated rejection (X\n 2<\/jats:sup>\n = 13.44; Log-rank=0.001 and\n X<\/jats:italic>\n 2<\/jats:sup>\n = 0.34; Log-rank=0.84). The combined effect of two\n MICA<\/jats:italic>\n allele mismatches and\n rs1049174[GG]<\/jats:italic>\n genotype shows the highest risk (X\n 2<\/jats:sup>\n = 23.21; Log-rank&lt;0.001). Most importantly, patients with\n rs1049174[GG]<\/jats:italic>\n and\n rs2255336[<\/jats:italic>\n AA\n ]<\/jats:italic>\n genotypes may respond less to mTOR inhibitor immunosuppressive therapy than Calcineurin inhibitors (\n rs1049174[GG];<\/jats:italic>\n P=0.035; and\n rs2255336[AA]<\/jats:italic>\n ; P=0.002).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Recipient\/donor\n MICA<\/jats:italic>\n allele mismatches and specific\n NKG2D<\/jats:italic>\n variants, as well as their combinations, influence kidney transplant outcomes, providing insights for personalized treatment and enhancing graft survival.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1440887","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T01:12:14Z","timestamp":1730941934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["MICA and NKG2D gene polymorphisms influence graft survival, 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