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
Year: 2015
Type: article
Study design: Observational Study
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.
Source: PLoS ONE
Authors: Víctor Noriega, Carolina Martínez-Laperche, Elena Buces, Marjorie Pion, Noemí Sánchez-Hernández, Beatriz Martín-Antonio, Vicent Guillem, Anna Bosch-Vizcaya, Leyre Bento, Milagros González-Rivera, Pascual Balsalobre, Mi Kwon, David Serrano, Jorge Gayoso, Rafael de la Cámara, Salut Brunet, Rafael Rojas-Contreras, José B. Nieto, Carmen Martínez, Marcos Gónzalez, Ildefonso Espigado, Juan C. Vallejo, Antonia Sampol, Antonio Jiménez-Velasco, Alvaro Urbano-Ispizua, Carlos Solano, David Gallardo, José L. Díez-Martín, Ismael Buño, Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
Institutions: Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Universitat de València, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Institut d'Investigació Biomèdica de Girona, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Universitario de La Princesa, Hospital de Sant Pau, Hospital Universitario Reina Sofía, Hospital General Universitario Morales Meseguer, Complejo Hospitalario de Salamanca, Hospital Universitario Virgen del Rocío, Hospital Universitario Central de Asturias, Hospital Universitario Son Espases, Hospital Regional Universitario de Málaga
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
OpenAlex ID: W2225633802