Common variants in NLRP2and NLRP3genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation

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 NLRP2and NLRP3were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3was associated with disease relapse (odds ratio (OR) = 6.3, P= 1 × 10−7), and donor GG genotype at rs1043684 in NLRP2was 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 NLRP1was 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, NLRPsgenotype would become an important factor in donor selection.