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, VictorMartínez-Laperche, CarolinaBuces, ElenaPion, MarjorieSánchez-Hernández, NoemíMartín-Antonio, BeatrizGuillem, VicentBosch-Vizcaya, AnnaBento, LeyreGonzález Rivera, MilagrosBalsalobre, PascualKwon, MiSerrano, DavidGayoso, JorgeCámara, Rafael de laBrunet, SalutRojas-Contreras, RafaelNieto, José B.Martínez, CarmenGónzalez, MarcosEspigado, IldefonsoVallejo, CarlosSampol, AntoniaJiménez-Velasco, AntonioUrbano Ispizua, ÁlvaroSolano, CarlosGallardo, DavidDíez-Martín, José L.Buño, IsmaelSpanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)2016-07-252016-07-252015-10-161932-6203https://hdl.handle.net/2445/100940The 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.11 p.application/pdfengcc-by (c) Noriega et al., 2015http://creativecommons.org/licenses/by/3.0/esLimfòcitsCèl·lules TCèl·lules mareLymphocytesT cellsStem cellsThe 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 Transplantationinfo:eu-repo/semantics/article6599742016-07-25info:eu-repo/semantics/openAccess26473355