학술논문
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.
Document Type
article
Author
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)
Source
PLoS ONE, Vol 10, Iss 10, p e0140454 (2015)
Subject
Language
English
ISSN
1932-6203
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.