Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation

被引：34

作者：

Granell, Miquel ^{[1
]}

Urbano-Ispizua, Alvaro ^{[1
]}

Pons, Aina ^{[2
]}

Ignacio Arosgtegui, Juan ^{[3
]}

Gel, Bernat ^{[4
]}

Navarro, Alfons ^{[2
]}

Jansa, Sonia ^{[2
]}

Artells, Rosa ^{[2
]}

Gaya, Anna ^{[1
]}

Talarn, Carme ^{[1
]}

Fernandez-Avilles, Francesc ^{[1
]}

Martinez, Carmen ^{[1
]}

Rovira, Montserrat ^{[1
]}

Carreras, Enric ^{[1
]}

Rozman, Ciril ^{[1
]}

Juan, Manel ^{[3
]}

Yague, Jordi ^{[3
]}

Montserrat, Emili ^{[1
]}

Monzo, Mariano ^{[2
]}

机构：

[1] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Dept Hematol, Barcelona, Spain

[2] Univ Barcelona, Dept Anat & Embryol, Barcelona, Spain

[3] Hosp Clin Barcelona, Dept Immunol, Barcelona, Spain

[4] Tech Univ Catalonia, Comp Syst Dept, Barcelona, Spain

来源：

BLOOD | 2008年 / 112卷 / 10期

关键词：

D O I：

10.1182/blood-2007-12-129247

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1 beta (IL-1 beta) 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 = 10 = 7), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 = 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. (Blood. 2008; 112: 4337-4342)

引用

页码：4337 / 4342

页数：6

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