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, Víctor (Hospital General Universitario Gregorio Marañón)
Martínez-Laperche, Carolina (Hospital General Universitario Gregorio Marañón)
Buces, Elena (Hospital General Universitario Gregorio Marañón)
Pion, Marjorie (Hospital General Universitario Gregorio Marañón)
Sánchez-Hernández, Noemi (Hospital General Universitario Gregorio Marañón)
Martín-Antonio, B (Hospital Clínic i Provincial de Barcelona)
Guillem, Vicent (Universitat de València)
Bosch-Vizcaya, Anna (Hospital Universitari de Girona Doctor Josep Trueta)
Bento, Leyre (Hospital General Universitario Gregorio Marañón)
González-Rivera, Milagros (Hospital General Universitario Gregorio Marañón)
Balsalobre, Pascual (Hospital General Universitario Gregorio Marañón)
Kwon, Mi (Hospital General Universitario Gregorio Marañón)
Serrano Simonneau, David (Hospital General Universitario Gregorio Marañón)
Gayoso, Jorge (Hospital General Universitario Gregorio Marañón)
de la Camara, Rafael (Hospital Universitario de la Princesa (Madrid))
Brunet, Salut (Institut d'Investigació Biomèdica Sant Pau)
Rojas-Contreras, Rafael (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Nieto, José B. (Hospital General Universitario Morales Meseguer (Múrcia))
Martínez, Carmen (Hospital Clínic i Provincial de Barcelona)
González, Marcos (Hospital Universitario de Salamanca)
Espigado, Ildefonso (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Vallejo, Juan C. (Hospital Universitario Central de Asturias)
Sampol, Antonia (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Jiménez-Velasco, Antonio (Hospital Regional Universitario de Málaga)
Urbano Ispizua, Álvaro (Hospital Clínic i Provincial de Barcelona)
Solano, Carlos (Universitat de València)
Gallardo, David (Hospital Universitari de Girona Doctor Josep Trueta)
Díez-Martín, José L. (Hospital General Universitario Gregorio Marañón)
Buño, Ismael (Hospital General Universitario Gregorio Marañón)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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:.
Ajuts:	Ministerio de Ciencia e Innovación PI11-00708 Ministerio de Economía y Competitividad PI14-01731
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	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
Publicat a:	PloS one, Vol. 10 Núm. 10 (16 2015) , p. e0140454, ISSN 1932-6203

DOI: 10.1371/journal.pone.0140454
PMID: 26473355

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