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, 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

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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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

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spelling	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 TransplantationNoriega, 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 TrFactores 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 HomólogoForkhead Transcription FactorsGenotypeAgedYoung AdultHematopoietic Stem Cell TransplantationTransplantation, HomologousAdultHumansGraft vs Leukemia EffectMiddle AgedPromoter Regions, GeneticGraft vs Host DiseaseMaleTissue DonorsFemaleGenetic Association StudiesSurvival AnalysisPolymorphism, GeneticThe 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.Public Library of Science (PLOS)20242024-07-0420152015-10-1620152015-10-16research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/20154reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/201542026-06-12T12:43:37Z
dc.title.none.fl_str_mv	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
title	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
spellingShingle	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, Victor 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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
dc.creator.none.fl_str_mv	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
author	Noriega, Victor
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	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
topic	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
description	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.
publishDate	2015
dc.date.none.fl_str_mv	2015 2015-10-16 2015 2015-10-16 2024 2024-07-04
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/20154
url	http://hdl.handle.net/20.500.12105/20154
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Public Library of Science (PLOS)
publisher.none.fl_str_mv	Public Library of Science (PLOS)
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,81155

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

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