6533b7d7fe1ef96bd1268581
RESEARCH PRODUCT
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.
Víctor NoriegaCarolina Martínez-lapercheElena BucesMarjorie PionMarjorie PionNoemí Sánchez-hernándezBeatriz Martín-antonioVicent GuillemAnna Bosch-vizcayaLeyre BentoMilagros González-riveraPascual BalsalobreMi KwonDavid SerranoJorge GayosoRafael De La CámaraSalut BrunetRafael Rojas-contrerasJosé B NietoCarmen MartínezMarcos GónzalezIldefonso EspigadoJuan C VallejoAntonia SampolAntonio Jiménez-velascoAlvaro Urbano-ispizuaCarlos SolanoDavid GallardoJosé L Díez-martínIsmael BuñoSpanish Hematopoietic Stem Cell Transplantation And Cell Therapy Group (Geth)subject
MaleAnálisis de supervivenciatrasplante de células madre hematopoyéticasmedicine.medical_treatmenthumanos:Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis [Medical Subject Headings]Graft vs Host Diseaselcsh:MedicinePolimorfismo genético:Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings]Hematopoietic stem cell transplantationStem cellsRegiones promotoras genéticas:Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies [Medical Subject Headings]:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]Trasplante homólogoIL-2 receptorLymphocytesMasculinoPromoter Regions Geneticlcsh:Sciencemediana edadancianoMultidisciplinaryAdultoFemenino:Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell Transplantation [Medical Subject Headings]Hematopoietic Stem Cell TransplantationFOXP3Forkhead Transcription Factorsadultoanálisis de supervivenciaMiddle AgedTissue DonorsHumanosestudios de asociación genéticaadulto jovenmedicine.anatomical_structuresurgical procedures operativeCèl·lules T:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Transcription Factors::Winged-Helix Transcription Factors::Forkhead Transcription Factors [Medical Subject Headings]Female:Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings]Factores de transcripción en cabeza de tenedorCèl·lules mareTrasplante de células madre hematopoyéticasResearch ArticleAdult:Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings]GenotypeGraft-vs-Leukemia EffectRegulatory T cellAncianoT cells:Check Tags::Male [Medical Subject Headings]Graft vs Leukemia Effectfactores de transcripción en cabeza de tenedorHuman leukocyte antigenBiologyEnfermedad injerto contra huéspedLimfòcitsYoung AdultDonantes de tejidos:Named Groups::Persons::Tissue Donors [Medical Subject Headings]:Named Groups::Persons::Age Groups::Adult [Medical Subject Headings]medicineHumansTransplantation Homologous:Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings]Genetic Association StudiesAgedMediana edadTransplantationPolymorphism GeneticEstudios de asociación genéticaEfecto injerto contra leucemialcsh:Rdonantes de tejidostrasplante:Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic [Medical Subject Headings]medicine.diseaseSurvival Analysis:Diseases::Immune System Diseases::Graft vs Host Disease [Medical Subject Headings]Transplantation:Analytical Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures Operative::Transplantation::Transplantation Homologous [Medical Subject Headings]efecto injerto contra leucemiaGraft-versus-host disease:Check Tags::Female [Medical Subject Headings]Immunology:Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Graft vs Host Reaction::Graft vs Tumor Effect::Graft vs Leukemia Effect [Medical Subject Headings]enfermedad injerto contra huésped:Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements Transcriptional::Promoter Regions Genetic [Medical Subject Headings]lcsh:QgenotipoGenotipodescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-10-16 | PLoS ONE |