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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1440887
This article is part of the Research Topic Antibody-Mediated Rejection After Solid Organ Transplantation View all 6 articles
MICA and NKG2D Gene Polymorphisms Influence Graft Survival, and Response to Therapy in Kidney Transplantation
Provisionally accepted- 1 Complex Structure of Medical Genetics, R. Binaghi Hospital, Local Public Health and Social Care Unit (ASSL) of Cagliari., Cagliari, Sardinia, Italy
- 2 Associazione per l’Avanzamento della Ricerca per i Trapianti (AART), Cagliari, Sardinia, Italy
- 3 Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
- 4 Section of Pathology, Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, Sardinia, Italy
- 5 Centre for Research University Services (CeSAR, Centro Servizi di Ateneo per la Ricerca), University of Cagliari, Monserrato, Italy
- 6 Other, Cagliari, Italy
- 7 Complex Structure of Medical Genetics, R.Binaghi Hospital, Cagliari, Sardinia, Italy
- 8 Department of Anatomic Pathology, G. Brotzu Hospital, Cagliari, Sardinia, Italy
- 9 Department of Pathological Anatomy, ARNAS, S. Michele Hospital, Cagliari, Sardinia, Italy
- 10 Pneumology Unit, R. Binaghi Hospital, ASSL Cagliari, Cagliari, Italy
- 11 Department of Medical Sciences and Public Health, Faculty of Medicine and Surgery, University of Cagliari, Cagliari, Sardinia, Italy
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.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.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).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.
Keywords: Kidney transplant, Antibody-mediated Rejection, MICA, NKG2D, dsa
Received: 30 May 2024; Accepted: 18 Oct 2024.
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. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Roberto Littera, Complex Structure of Medical Genetics, R. Binaghi Hospital, Local Public Health and Social Care Unit (ASSL) of Cagliari., Cagliari, Sardinia, Italy
STEFANO MOCCI, Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
Davide Argiolas, Other, Cagliari, Italy
Letizia Littarru, Other, Cagliari, Italy
Sara Lai, Complex Structure of Medical Genetics, R.Binaghi Hospital, Cagliari, Sardinia, Italy
Celeste Sanna, Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
Caterina Mereu, Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
Michela Lorrai, Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
Andrea Angioi, Other, Cagliari, Italy
Giacomo Mascia, Other, Cagliari, Italy
Valeria Matta, Other, Cagliari, Italy
Matteo Floris, Other, Cagliari, Italy
Cristina Manieli, Department of Anatomic Pathology, G. Brotzu Hospital, Cagliari, 09134, Sardinia, Italy
Daniela Onnis, Department of Pathological Anatomy, ARNAS, S. Michele Hospital, Cagliari, Sardinia, Italy
Stefania Rassu, Complex Structure of Medical Genetics, R.Binaghi Hospital, Cagliari, Sardinia, Italy
Silvia Deidda, Pneumology Unit, R. Binaghi Hospital, ASSL Cagliari, Cagliari, Italy
Mauro Carta, Department of Medical Sciences and Public Health, Faculty of Medicine and Surgery, University of Cagliari, Cagliari, 09124, Sardinia, Italy
Erika Giuressi, Complex Structure of Medical Genetics, R.Binaghi Hospital, Cagliari, Sardinia, Italy
Sabrina Giglio, Medical Genetics Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Sardinia, Italy
Antonello Pani, Department of Medical Sciences and Public Health, Faculty of Medicine and Surgery, University of Cagliari, Cagliari, 09124, Sardinia, Italy
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