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.
abstract: 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.
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Noriega
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Laperche
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Buces
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Department of Inmunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Sánchez-Hernández
authors.affiliation: Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Instituto de Investigación Josep Carreras (IJC), Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Antonio
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Guillem
authors.affiliation: Department of Hematology, ICO Girona, Hospital Josep Trueta, IDIBGI Foundation, Girona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Bosch-Vizcaya
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Bento
authors.affiliation: Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; DNA Sequencing Core Facility, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: González-Rivera
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Balsalobre
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Mi
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gayoso
authors.affiliation: Department of Hematology, Hospital La Princesa, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Cámara
authors.affiliation: Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Department of Hematology, Hospital Reina Sofia, Cordoba, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rojas-Contreras
authors.affiliation: Department of Hematology, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: José B
authors.initials: JB
authors.lastname: Nieto
authors.affiliation: Department of Hematology, Hospital Clínic, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Gónzalez
authors.affiliation: Department of Hematology and Hemotherapy, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Espigado
authors.affiliation: Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Vallejo
authors.affiliation: Department of Hematology, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sampol
authors.affiliation: Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Velasco
authors.affiliation: Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Instituto de Investigación Josep Carreras (IJC), Barcelona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.affiliation: Department of Hematology, ICO Girona, Hospital Josep Trueta, IDIBGI Foundation, Girona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Díez-Martín
authors.affiliation: Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Buño
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000235:genetics*; D020544:Graft vs Leukemia Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors