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dc.contributor.author | Sánchez-Maldonado, Jose Manuel | |
dc.contributor.author | Moñiz-Díez, Ana | |
dc.contributor.author | Ter Horst, Rob | |
dc.contributor.author | Campa, Daniele | |
dc.contributor.author | Cabrera-Serrano, Antonio José | |
dc.contributor.author | Martínez-Bueno, Manuel | |
dc.contributor.author | Garrido-Collado, María Del Pilar | |
dc.contributor.author | Hernández-Mohedo, Francisca | |
dc.contributor.author | Fernández-Puerta, Laura | |
dc.contributor.author | López-Nevot, Miguel Ángel | |
dc.contributor.author | Cunha, Cristina | |
dc.contributor.author | González-Sierra, Pedro Antonio | |
dc.contributor.author | Springer, Jan | |
dc.contributor.author | Lackner, Michaela | |
dc.contributor.author | Alcazar-Fuoli, Laura | |
dc.contributor.author | Fianchi, Luana | |
dc.contributor.author | Aguado, José María | |
dc.contributor.author | Pagano, Livio | |
dc.contributor.author | López-Fernández, Elisa | |
dc.contributor.author | Clavero, Esther | |
dc.contributor.author | Potenza, Leonardo | |
dc.contributor.author | Luppi, Mario | |
dc.contributor.author | Moratalla, Lucia | |
dc.contributor.author | Solano, Carlos | |
dc.contributor.author | Sampedro, Antonio | |
dc.contributor.author | Cuenca-Estrella, Manuel | |
dc.contributor.author | Lass-Flörl, Cornelia | |
dc.contributor.author | PCRAGA Study Group | |
dc.contributor.author | Canzian, Federico | |
dc.contributor.author | Loeffler, Juergen | |
dc.contributor.author | Li, Yang | |
dc.contributor.author | Einsele, Hermann | |
dc.contributor.author | Netea, Mihai G | |
dc.contributor.author | Vázquez, Lourdes | |
dc.contributor.author | Carvalho, Agostinho | |
dc.contributor.author | Jurado, Manuel | |
dc.contributor.author | Sainz, Juan | |
dc.date.accessioned | 2021-01-27T08:46:07Z | |
dc.date.available | 2021-01-27T08:46:07Z | |
dc.date.issued | 2020-12-23 | |
dc.identifier.citation | J Fungi (Basel). 2020 Dec 23;7(1):4. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/11684 | |
dc.description.abstract | Here, 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.sponsorship | This 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.language.iso | eng | es_ES |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B cells | es_ES |
dc.subject | MAPKAPK2 | es_ES |
dc.subject | TNFSF14 | es_ES |
dc.subject | TNFSF4 | es_ES |
dc.subject | TSLP | es_ES |
dc.subject | Genetic susceptibility | es_ES |
dc.subject | Invasive aspergillosis | es_ES |
dc.subject | Monocytes | es_ES |
dc.subject | Serum biomarkers | es_ES |
dc.title | Polymorphisms 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.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 33374839 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 1 | es_ES |
dc.identifier.doi | 10.3390/jof7010004 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Fundação para a Ciência e Tecnologia (Portugal) | |
dc.contributor.funder | Unión Europea | |
dc.contributor.funder | Fundación La Caixa | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2309-608X | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/jof7010004 | es_ES |
dc.identifier.journal | Journal of fungi (Basel, Switzerland) | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI20/01845 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/PI12/02688 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/ISCIII-FEDER PI17/02276 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/847507 | es_ES |
dc.rights.accessRights | open access | es_ES |
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INCLIVA - Instituto de Investigación Sanitaria Fundación para la Investigación del Hospital Clínico de Valencia (C. Valenciana)
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Centro Nacional de Microbiología (CNM)
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i+12 - Instituto de Investigación Hospital 12 de Octubre (Madrid)
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ibs.GRANADA - Instituto de Investigación Biosanitaria de Granada (Andalucía)