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

The 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...

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Detalles Bibliográficos
Autores: Noriega, Víctor, Martínez-Laperche, Carolina, Buces, Elena, Pion, Marjorie, Sánchez-Hernández, Noemi, Martín-Antonio, B|||0000-0003-0612-2693, Guillem, Vicent, Bosch-Vizcaya, Anna, Bento, Leyre|||0000-0001-9929-8617, González-Rivera, Milagros, Balsalobre, Pascual, Kwon, Mi|||0000-0002-3855-7774, Serrano Simonneau, David, Gayoso, Jorge, de la Camara, Rafael|||0000-0002-8189-5779, Brunet, Salut|||0000-0003-0491-1672, Rojas-Contreras, Rafael, Nieto, José B., Martínez, Carmen|||0000-0002-8401-7306, González, Marcos, Espigado, Ildefonso|||0000-0002-4043-6613, Vallejo, Juan C., Sampol, Antonia|||0000-0001-7465-6203, Jiménez-Velasco, Antonio|||0000-0001-6421-7872, Urbano Ispizua, Álvaro|||0000-0002-7529-9399, Solano, Carlos|||0000-0003-3702-0817, Gallardo, David|||0000-0003-1615-4592, Díez-Martín, José L., Buño, Ismael|||0000-0003-4931-9170
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:296542
Acceso en línea:https://ddd.uab.cat/record/296542
https://dx.doi.org/urn:doi:10.1371/journal.pone.0140454
Access Level:acceso abierto
Palabra clave:Adult
Aged
Female
Forkhead Transcription Factors
Genetic Association Studies
Genotype
Graft vs Host Disease
Graft vs Leukemia Effect
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Polymorphism, Genetic
Promoter Regions, Genetic
Survival Analysis
Tissue Donors
Transplantation, Homologous
Young Adult
Descripción
Sumario:The 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) 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. Copyright:

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