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Blood, 1 July 2007, Vol. 110, No. 1, pp. 461-467. Prepublished online as a Blood First Edition Paper on March 23, 2007; DOI 10.1182/blood-2007-01-069781. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-01-069781v1 110/1/461    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pérez-García, A. Articles by Gallardo, D. Search for Related Content PubMed PubMed Citation Articles by Pérez-García, A. Articles by Gallardo, D. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors. Arianne Pérez-García1, Rafael De la Cámara1, Jose Román-Gómez1, Antonio Jiménez-Velasco1, Maite Encuentra1, Jose B. Nieto1, Javier de la Rubia1, Alvaro Urbano-Ispizúa1, Salut Brunet1, Arturo Iriondo1, Marcos González1, David Serrano1, Ildefonso Espigado1, Carlos Solano1, Josep M. Ribera1, Josep M. Pujal1, Montserrat Hoyos1, David Gallardo1, and the GVHD/Immunotherapy Committee of the Spanish Group of Hematopoietic Stem Cell Transplantation1 1 Clinical Hematology Department, Alloreactivity Unit, and Laborateri de Recerca Translacional, Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain CTLA-4 is an inhibitory molecule that down-regulates T-cell activation. Although polymorphisms at CTLA-4 have been correlated with autoimmune diseases their association with clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has yet to be explored. A total of 5 CTLA-4 single-nucleotide polymorphisms were genotyped on 536 HLA-identical sibling donors of allo-HSC transplants. Genotypes were tested for an association with patients' posttransplantation outcomes. The effect of the polymorphisms on cytotoxic T-lymphocyte antigen 4 (CTLA-4) mRNA and protein production were determined in 60 healthy control participants. We observed a reduction in the mRNA expression of the soluble CTLA-4 isoform in the presence of a G allele at CT60 and +49. Patients receiving stem cells from a donor with at least 1 G allele in position CT60 had worse overall survival (56.2% vs 69.8% at 5 years; P = .001; hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.75-8.22), due to a higher risk of relapse (P = .049; HR, 1.71; 95% CI, 1.00-2.93). Acute graft-versus-host disease (aGVHD) was more frequent in patients receiving CT60 AA stem cells (P = .033; HR, 1.54; 95% CI, 1.03-2.29). This is the first study to report an association between polymorphisms at CTLA-4 and clinical outcome after allo-HSCT. The CT60 genotype influences relapse and aGVHD, probably due to its action on CTLA-4 alternative splicing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Azarian, M. Busson, V. Lepage, D. Charron, A. Toubert, P. Loiseau, R. P. de Latour, V. Rocha, and G. Socie Donor CTLA-4 +49 A/G*GG genotype is associated with chronic GVHD after HLA-identical haematopoietic stem-cell transplantations Blood, December 15, 2007; 110(13): 4623 - 4624. [Full Text] [PDF]

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