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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; Martínez-Laperche, Carolina; Buces, Elena; Pion, Marjorie; Sánchez-Hernández, Noemí; Martín-Antonio, Beatriz; Guillem, Vicent; Bosch-Vizcaya, Anna; Bento, Leyre; González-Rivera, Milagros; Balsalobre, Pascual; Kwon, Mi; Serrano, David; Gayoso, Jorge; de la Cámara, Rafael; Brunet, Salut; Rojas-Contreras, Rafael; Nieto, José B; Martínez, Carmen; Gónzalez, Marcos; Espigado, Ildefonso; Vallejo, Juan C; Sampol, Antonia; Jiménez-Velasco, Antonio; Urbano-Ispizua, Alvaro; Solano, Carlos; Gallardo, David; Díez-Martín, José L; Buño, Ismael.
Afiliação
  • Noriega V; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Martínez-Laperche C; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Buces E; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Pion M; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Department of Inmunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • Sánchez-Hernández N; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • Martín-Antonio B; Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Instituto de Investigación Josep Carreras (IJC), Barcelona, Spain.
  • Guillem V; Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
  • Bosch-Vizcaya A; Department of Hematology, ICO Girona, Hospital Josep Trueta, IDIBGI Foundation, Girona, Spain.
  • Bento L; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • González-Rivera M; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; DNA Sequencing Core Facility, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
  • Balsalobre P; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Kwon M; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Serrano D; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Gayoso J; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • de la Cámara R; Department of Hematology, Hospital La Princesa, Madrid, Spain.
  • Brunet S; Department of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
  • Rojas-Contreras R; Department of Hematology, Hospital Reina Sofia, Cordoba, Spain.
  • Nieto JB; Department of Hematology, Hospital Morales Meseguer, Murcia, Spain.
  • Martínez C; Department of Hematology, Hospital Clínic, Barcelona, Spain.
  • Gónzalez M; Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
  • Espigado I; Department of Hematology and Hemotherapy, Hospital Universitario Virgen del Rocío, Seville, Spain.
  • Vallejo JC; Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain.
  • Sampol A; Department of Hematology, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain.
  • Jiménez-Velasco A; Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain.
  • Urbano-Ispizua A; Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Instituto de Investigación Josep Carreras (IJC), Barcelona, Spain.
  • Solano C; Department of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Universitat de Valencia, Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
  • Gallardo D; Department of Hematology, ICO Girona, Hospital Josep Trueta, IDIBGI Foundation, Girona, Spain.
  • Díez-Martín JL; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
  • Buño I; Department of Hematology, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
PLoS One ; 10(10): e0140454, 2015.
Article em En | MEDLINE | ID: mdl-26473355
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Transplante de Células-Tronco Hematopoéticas / Efeito Enxerto vs Leucemia / Fatores de Transcrição Forkhead / Doença Enxerto-Hospedeiro Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Transplante de Células-Tronco Hematopoéticas / Efeito Enxerto vs Leucemia / Fatores de Transcrição Forkhead / Doença Enxerto-Hospedeiro Idioma: En Ano de publicação: 2015 Tipo de documento: Article