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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 (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 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 Monzo, M. Search for Related Content PubMed PubMed Citation Articles by Granell, M. Articles by Monzo, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 17, 2007 Accepted August 6, 2008 Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation Miquel Granell, Alvaro Urbano-Ispizua*, Aina Pons, Juan Ignacio Arostegui, Bernat Gel, Alfons Navarro, Sonia Jansa, Rosa Artells, Anna Gaya, Carme Talarn, Francesc Fernandez-Aviles, Carmen Martinez, Montserrat Rovira, Enric Carreras, Ciril Rozman, Manel Juan, Jordi Yague, Emili Montserrat, and Mariano Monzo Hematology Department, Hospital Clinic of Barcelona. IDIBAPS, Barcelona, Spain Anatomy and Embriology Departments, University of Barcelona, Barcelona, Spain Immunology Department, Hospital Clinic of Barcelona, Barcelona, Spain Computing Systems Department, Technical University of Catalonia, Barcelona, Spain * Corresponding author; email: alvaro.urbano.sspa{at}juntadeandalucia.es. The inflammasomes are macromolecular cytosolic complexes involved in the production of IL-1 and IL-18 in response to several pathogen-derived stimuli. Such interleukines have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analysed 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 five genes of the inflammasome, namely NLRP1, NLRP2, NLRP3, CARD8 and CASP5 were genotyped in 133 HLA-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 (OR 6.3, p=1x10-7) and donor GG genotype at rs1043684 in NLRP2 was associated with non-relapse mortality (NRM) (OR 4.4, p=6x10-4) and overall survival (OS) (OR 3.1, p=0.0001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with NRM (OR 2.8, p=0.005) and OS (OR 2.0, p=0.009). 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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