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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4337-4342. Prepublished online as a Blood First Edition Paper on September 4, 2008; DOI 10.1182/blood-2007-12-129247. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-12-129247v1 112/10/4337    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Granell, M. Articles by Monzó, M. Search for Related Content PubMed PubMed Citation Articles by Granell, M. Articles by Monzó, M. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation Miquel Granell1, Álvaro Urbano-Ispizua1, Aina Pons2, Juan Ignacio Aróstegui3, Bernat Gel4, Alfons Navarro2, Sonia Jansa2, Rosa Artells2, Anna Gaya1, Carme Talarn1, Francesc Fernández-Avilés1, Carmen Martínez1, Montserrat Rovira1, Enric Carreras1, Ciril Rozman1, Manel Juan3, Jordi Yagüe3, Emili Montserrat1, and Mariano Monzó2 1 Hematology Department, Hospital Clínic of Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona; 2 Anatomy and Embriology Department, University of Barcelona, Barcelona; 3 Immunology Department, Hospital Clínic of Barcelona, Barcelona; and 4 Computing Systems Department, Technical University of Catalonia, Barcelona, Spain The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1β (IL-1β) and IL-18 in response to several pathogen-derived stimuli. Such interleukins have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analyzed the relationship between the interindividual variability in inflammasome protein-encoding genes in donors and patients and clinical outcome after allo-SCT. Fourteen common genetic variants in 5 genes of the inflammasome, namely, NLRP1, NLRP2, NLRP3, CARD8, and CASP5, were genotyped in 133 human leukocyte antigen-identical sibling pairs undergoing allo-SCT. In the multivariate analysis, donor variants in NLRP2 and NLRP3 were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3 was associated with disease relapse (odds ratio (OR) = 6.3, P = 1 x 10–7), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 x 10–4) and overall survival (OR = 3.1, P = .001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with nonrelapse mortality (OR = 2.8, P = .005) and overall survival (OR = 2.0, P = .009). These results suggest that inflammasome genetic variants are important prognostic factors for the outcome of allo-SCT. If validated in larger studies, including unrelated allo-SCT, NLRPs genotype would become an important factor in donor selection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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