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dc.contributor.authorSánchez-Maldonado, Jose Manuel
dc.contributor.authorMoñiz-Díez, Ana
dc.contributor.authorTer Horst, Rob
dc.contributor.authorCampa, Daniele
dc.contributor.authorCabrera-Serrano, Antonio José
dc.contributor.authorMartínez-Bueno, Manuel
dc.contributor.authorGarrido-Collado, María Del Pilar
dc.contributor.authorHernández-Mohedo, Francisca
dc.contributor.authorFernández-Puerta, Laura
dc.contributor.authorLópez-Nevot, Miguel Ángel
dc.contributor.authorCunha, Cristina
dc.contributor.authorGonzález-Sierra, Pedro Antonio
dc.contributor.authorSpringer, Jan
dc.contributor.authorLackner, Michaela
dc.contributor.authorAlcazar-Fuoli, Laura 
dc.contributor.authorFianchi, Luana
dc.contributor.authorAguado, José María
dc.contributor.authorPagano, Livio
dc.contributor.authorLópez-Fernández, Elisa
dc.contributor.authorClavero, Esther
dc.contributor.authorPotenza, Leonardo
dc.contributor.authorLuppi, Mario
dc.contributor.authorMoratalla, Lucia
dc.contributor.authorSolano, Carlos
dc.contributor.authorSampedro, Antonio
dc.contributor.authorCuenca-Estrella, Manuel 
dc.contributor.authorLass-Flörl, Cornelia
dc.contributor.authorPcraga Study Group, null
dc.contributor.authorCanzian, Federico
dc.contributor.authorLoeffler, Juergen
dc.contributor.authorLi, Yang
dc.contributor.authorEinsele, Hermann
dc.contributor.authorNetea, Mihai G
dc.contributor.authorVázquez, Lourdes
dc.contributor.authorCarvalho, Agostinho
dc.contributor.authorJurado, Manuel
dc.contributor.authorSainz, Juan
dc.identifier.citationJ Fungi (Basel) . 2020 Dec 23;7(1):4.es_ES
dc.description.abstractHere, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungicidal activity (p = 0.048). In addition, we observed that each copy of the MAPKAPK2rs12137965G allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2rs17013271T allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2rs12137965G allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (p = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (p = 0.00097). Finally, we also found that carriers of the protective MAPKAPK2rs17013271T allele had decreased numbers of CD27-IgM-IgD- B cells (p = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (p = 0.00018 and 0.00023). Altogether, these results suggest a role of the TNFSF4 and MAPKAPK2 genes in determining IA risk.es_ES
dc.description.sponsorshipThis study was supported by grants PI20/01845, PI12/02688, and ISCIII-FEDER PI17/02276 from Fondo de Investigaciones Sanitarias (Madrid, Spain), PIM2010EPA-00756 from the ERA-NET PathoGenoMics (0315900A), the Collaborative Research Center/Transregio 124 FungiNet, the Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-SER/29635/2017, PTDC/MED-GEN/28778/2017, CEECIND/03628/2017, and CEECIND/04058/2018), the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HP17/52190003).es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectB cellses_ES
dc.subjectgenetic susceptibilityes_ES
dc.subjectinvasive aspergillosises_ES
dc.subjectserum biomarkerses_ES
dc.titlePolymorphisms within the TNFSF4 and MAPKAPK2 Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.es_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderFondo de Investigaciones Sanitariases_ES
dc.contributor.funderFundação para a Ciência e a Tecnologia (Portugal)es_ES
dc.contributor.funderEuropean Uniones_ES
dc.contributor.funderFundación La Caixaes_ES
dc.identifier.journalJournal of fungi (Basel, Switzerland)es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ISCIII-FEDER PI17/02276es_ES

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Atribución 4.0 Internacional
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