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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 (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 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 Perez-Garcia, A. Articles by Gallardo, D. Search for Related Content PubMed PubMed Citation Articles by Perez-Garcia, A. Articles by Gallardo, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 24, 2007 Accepted March 19, 2007 CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors Arianne Perez-Garcia, Rafael De la Camara, Jose Roman-Gomez, Antonio Jimenez-Velasco, Maite Encuentra, Jose B. Nieto, Javier de la Rubia, Alvaro Urbano-Ispizua, Salut Brunet, Arturo Iriondo, Marcos Gonzalez, David Serrano, Ildefonso Espigado, Carlos Solano, Josep M. Ribera, Josep M. Pujal, Montserrat Hoyos, and David Gallardo* Alloreactivity Unit, Laboratori de Recerca Translacional, and Clinical Hematology Department, Institut Catala d'Oncologia-IDIBELL, Hospital Duran i Reynals, Barcelona, Spain * Corresponding author; email: 27532dgg{at}comb.es. CTLA-4 is an inhibitory molecule that downregulates 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. Five CTLA-4 single-nucleotide polymorphisms were genotyped on 536 HLA-identical sibling donors of allo-HSCT. Genotypes were tested for an association with patients' post-transplant outcome. The effect of the polymorphisms on CTLA-4 mRNA and protein production were determined in 60 healthy controls. 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 one G allele in position CT60 had worse overall survival (56.2% vs. 69.8% at 5 years; p: 0.001; HR: 3.80; 95% CI: 1.75-8.22), due to a higher risk of relapse (p: 0.049; 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: 0.033; 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 post allo-HSCT. 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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