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, Victor, Martinez-Laperche, Carolina, Buces, Elena, Sanchez-Hernandez, Noemi, Martin-Antonio, Beatriz, Guillem, Vicent, Bosch-Vizcaya, Anna, Bento, Leyre, Gonzalez-Rivera, Milagros, Balsalobre, Pascual, Kwon, Mi, Serrano, David, Gayoso, Jorge, de la Cámara, Rafael, Brunet, Salut, Rojas-Contreras, Rafael, Nieto, Jose B., Martinez, Carmen, Gonzalez, Marcos, Espigado, Ildefonso, Vallejo, Juan C., Sampol Mayol, Antonia, Jimenez-Velasco, Antonio, Urbano-Ispizua, Alvaro, Solano, Carlos, Gallardo, David, Diez-Martin, Jose L, Buno, Ismael, Spanish Hematopoietic Stem Cell Tr
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/20154
Acceso en línea:http://hdl.handle.net/20.500.12105/20154
Access Level:acceso abierto
Palabra clave:Factores de Transcripción Forkhead
Efecto Injerto vs Leucemia
Análisis de Supervivencia
Enfermedad Injerto contra Huésped
Donantes de Tejidos
Femenino
Masculino
Trasplante de Células Madre Hematopoyéticas
Humanos
Persona de Mediana Edad
Adulto Joven
Estudios de Asociación Genética
Regiones Promotoras Genéticas
Anciano
Genotipo
Adulto
Polimorfismo Genético
Trasplante Homólogo
Forkhead Transcription Factors
Genotype
Aged
Young Adult
Hematopoietic Stem Cell Transplantation
Transplantation, Homologous
Adult
Humans
Graft vs Leukemia Effect
Middle Aged
Promoter Regions, Genetic
Graft vs Host Disease
Male
Tissue Donors
Female
Genetic Association Studies
Survival Analysis
Polymorphism, Genetic
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)(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.

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