The Genotype of the Donor for the (GT)(n) Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

Noriega, VictorMartinez-Laperche, CarolinaBuces, ElenaSanchez-Hernandez, NoemiMartin-Antonio, BeatrizGuillem, VicentBosch-Vizcaya, AnnaBento, LeyreGonzalez-Rivera, MilagrosBalsalobre, PascualKwon, MiSerrano, DavidGayoso, Jorgede la Cámara, RafaelBrunet, SalutRojas-Contreras, RafaelNieto, Jose B.Martinez, CarmenGonzalez, MarcosEspigado, IldefonsoVallejo, Juan C.Sampol Mayol, AntoniaJimenez-Velasco, AntonioUrbano-Ispizua, AlvaroSolano, CarlosGallardo, DavidDiez-Martin, Jose LBuno, IsmaelSpanish Hematopoietic Stem Cell Tr2024-07-042024-07-042015-10-16Noriega V, Martinez-Laperche C, Buces E, Pion M, Sanchez-Hernandez N, Martin-Antonio B, et al. The Genotype of the Donor for the (GT)(n) Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation. PLoS One. 2015 Oct 16;10(10):e0140454.1932-6203http://hdl.handle.net/20.500.13003/10659http://hdl.handle.net/20.500.12105/20154The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (<=(GT)(15)) for the (GT)(n) polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto-or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients.enghttp://creativecommons.org/licenses/by/4.0/Forkhead Transcription FactorsGenotypeAgedYoung AdultHematopoietic Stem Cell TransplantationTransplantation, HomologousAdultHumansGraft vs Leukemia EffectMiddle AgedPromoter Regions, GeneticGraft vs Host DiseaseMaleTissue DonorsFemaleGenetic Association StudiesSurvival AnalysisPolymorphism, GeneticThe Genotype of the Donor for the (GT)(n) Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantationresearch articleAttribution 4.0 International264733551010e014045410.1371/journal.pone.0140454PloS Oneopen accessFactores de Transcripción ForkheadEfecto Injerto vs LeucemiaAnálisis de SupervivenciaEnfermedad Injerto contra HuéspedDonantes de TejidosFemeninoMasculinoTrasplante de Células Madre HematopoyéticasHumanosPersona de Mediana EdadAdulto JovenEstudios de Asociación GenéticaRegiones Promotoras GenéticasAncianoGenotipoAdultoPolimorfismo GenéticoTrasplante Homólogo2-s2.0-84949220859363185500054L607132865