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dc.contributor.authoránchez-Maldonado, Jose Manuel
dc.contributor.authorMoñiz-Díez, Ana
dc.contributor.authorRob Ter Horst, Daniele Campa
dc.contributor.authorCabrera-Serrano, Antonio José
dc.contributor.authorGarrido-Collado, María Del Pilar
dc.contributor.authorHernández-Mohedo, Fracisca
dc.contributor.authorFernández-Puerta, Laura
dc.contributor.authorLópez-Nevot, , Miguel Ángel
dc.contributor.authorCunha, Ctistina
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
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.date.accessioned2021-01-22T12:28:32Z
dc.date.available2021-01-22T12:28:32Z
dc.date.issued2020-12-23
dc.identifier.citation. J Fungi (Basel). 2020 Dec 23;7(1):E4. doi: 10.3390/jof7010004.en_US
dc.identifier.pmid33374839
dc.identifier.doi10.3390/jof7010004
dc.identifier.urihttp://hdl.handle.net/10033/622693
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.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectB cellsen_US
dc.subjectMAPKAPK2en_US
dc.subjectTNFSF14en_US
dc.subjectTNFSF4en_US
dc.subjectTSLPen_US
dc.subjectgenetic susceptibilityen_US
dc.subjectinvasive aspergillosisen_US
dc.subjectmonocytesen_US
dc.subjectserum biomarkersen_US
dc.titlePolymorphisms within the and Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.en_US
dc.typeArticleen_US
dc.identifier.eissn2309-608X
dc.contributor.departmentCiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.en_US
dc.identifier.journalJournal of fungi (Basel, Switzerland)en_US
dc.source.volume7
dc.source.issue1
refterms.dateFOA2021-01-22T12:28:33Z
dc.source.journaltitleJournal of fungi (Basel, Switzerland)
dc.source.countrySwitzerland


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