Frontiers in Immunology (Nov 2024)
MICA and NKG2D gene polymorphisms influence graft survival, and response to therapy in kidney transplantation
- Roberto Littera,
- Roberto Littera,
- Stefano Mocci,
- Stefano Mocci,
- Stefano Mocci,
- Davide Argiolas,
- Letizia Littarru,
- Sara Lai,
- Sara Lai,
- Maurizio Melis,
- Celeste Sanna,
- Caterina Mereu,
- Michela Lorrai,
- Alessia Mascia,
- Andrea Angioi,
- Giacomo Mascia,
- Valeria Matta,
- Nicola Lepori,
- Matteo Floris,
- Cristina Manieli,
- Paola Bianco,
- Daniela Onnis,
- Stefania Rassu,
- Silvia Deidda,
- Mauro Giovanni Carta,
- Erika Giuressi,
- Andrea Perra,
- Andrea Perra,
- Luchino Chessa,
- Luchino Chessa,
- Luchino Chessa,
- Sabrina Giglio,
- Sabrina Giglio,
- Sabrina Giglio,
- Antonello Pani,
- Antonello Pani
Affiliations
- Roberto Littera
- Medical Genetics, R. Binaghi Hospital, Cagliari, Italy
- Roberto Littera
- AART-ODV (Association for the Advancement of Research on Transplantation), Cagliari, Italy
- Stefano Mocci
- Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Stefano Mocci
- Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Stefano Mocci
- Center for Research University Services (CeSAR), (Centro Servizi di Ateneo per la Ricerca), University of Cagliari, Monserrato, Italy
- Davide Argiolas
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Letizia Littarru
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Sara Lai
- Medical Genetics, R. Binaghi Hospital, Cagliari, Italy
- Sara Lai
- AART-ODV (Association for the Advancement of Research on Transplantation), Cagliari, Italy
- Maurizio Melis
- AART-ODV (Association for the Advancement of Research on Transplantation), Cagliari, Italy
- Celeste Sanna
- Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Caterina Mereu
- Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Michela Lorrai
- Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Alessia Mascia
- Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Andrea Angioi
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Giacomo Mascia
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Valeria Matta
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Nicola Lepori
- Department of Medical Science and Public Health, University of Cagliari, Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Matteo Floris
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Cristina Manieli
- U.O. Anatomia Patologica, P.O. San Michele, ARNAS “G Brotzu”, Cagliari, Italy
- Paola Bianco
- U.O. Anatomia Patologica, P.O. San Michele, ARNAS “G Brotzu”, Cagliari, Italy
- Daniela Onnis
- U.O. Anatomia Patologica, P.O. San Michele, ARNAS “G Brotzu”, Cagliari, Italy
- Stefania Rassu
- Medical Genetics, R. Binaghi Hospital, Cagliari, Italy
- Silvia Deidda
- Pneumology Unit, R. Binaghi Hospital, ASSL Cagliari, Cagliari, Italy
- Mauro Giovanni Carta
- 0Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Erika Giuressi
- Medical Genetics, R. Binaghi Hospital, Cagliari, Italy
- Andrea Perra
- AART-ODV (Association for the Advancement of Research on Transplantation), Cagliari, Italy
- Andrea Perra
- Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Luchino Chessa
- AART-ODV (Association for the Advancement of Research on Transplantation), Cagliari, Italy
- Luchino Chessa
- 0Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Luchino Chessa
- 1Liver Unit, Department of Internal Medicine, University Hospital of Cagliari, Cagliari, Italy
- Sabrina Giglio
- Medical Genetics, R. Binaghi Hospital, Cagliari, Italy
- Sabrina Giglio
- Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
- Sabrina Giglio
- Center for Research University Services (CeSAR), (Centro Servizi di Ateneo per la Ricerca), University of Cagliari, Monserrato, Italy
- Antonello Pani
- Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu”, Cagliari, Italy
- Antonello Pani
- 2Department of Medical Science and Public Health, University of Cagliari, Nephrology, Dialysis and Transplantation Unit, ARNAS “G. Brotzu” Cagliari, Consiglio Nazionale delle Ricerche, Cagliari, Italy
- DOI
- https://doi.org/10.3389/fimmu.2024.1440887
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundAntibody-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.AimWe 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.MethodsOf 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.ResultsIncreased 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 X2 = 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).ConclusionRecipient/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
