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

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...

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Bibliographic Details
Published in:PloS one 2015-10, Vol.10 (10), p.e0140454
Main Authors: 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
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Antigens
Autoimmune diseases
Bone marrow
CD25 antigen
CD4 antigen
Cèl·lules mare
Cèl·lules T
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Female
Forkhead Transcription Factors - genetics
Foxp3 protein
Gene expression
Genetic Association Studies
Genotype
Genotypes
Graft rejection
Graft vs Host Disease - epidemiology
Graft vs Host Disease - genetics
Graft vs Leukemia Effect
Graft-versus-host reaction
Grafting
Hematology
Hematopoietic Stem Cell Transplantation - adverse effects
Histocompatibility antigen HLA
Hospitals
Humans
Immune system
Immunology
Immunoregulation
Incidence
Kidney transplantation
Leukemia
Limfòcits
Lymphocytes
Lymphocytes T
Male
Middle Aged
Multivariate analysis
Patients
Polymorphism
Polymorphism, Genetic
Preeclampsia
Promoter Regions, Genetic
Stem cell transplantation
Stem cells
Survival
Survival Analysis
T cells
Tissue Donors
Transcription factors
Transplantation
Transplantation, Homologous - adverse effects
Transplants
Transplants & implants
Young Adult
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0140454