Polymorphisms within the and Loci Influence the Risk of Developing Invasive Aspergillosis: A Two-Stage Case Control Study in the Context of the aspBIOmics Consortium.
dc.contributor.author | ánchez-Maldonado, Jose Manuel | |
dc.contributor.author | Moñiz-Díez, Ana | |
dc.contributor.author | Rob Ter Horst, Daniele Campa | |
dc.contributor.author | Cabrera-Serrano, Antonio José | |
dc.contributor.author | Garrido-Collado, María Del Pilar | |
dc.contributor.author | Hernández-Mohedo, Fracisca | |
dc.contributor.author | Fernández-Puerta, Laura | |
dc.contributor.author | López-Nevot, , Miguel Ángel | |
dc.contributor.author | Cunha, Ctistina | |
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 | 2021-01-22T12:28:32Z | |
dc.date.available | 2021-01-22T12:28:32Z | |
dc.date.issued | 2020-12-23 | |
dc.identifier.citation | . J Fungi (Basel). 2020 Dec 23;7(1):E4. doi: 10.3390/jof7010004. | en_US |
dc.identifier.pmid | 33374839 | |
dc.identifier.doi | 10.3390/jof7010004 | |
dc.identifier.uri | http://hdl.handle.net/10033/622693 | |
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. | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | B cells | en_US |
dc.subject | MAPKAPK2 | en_US |
dc.subject | TNFSF14 | en_US |
dc.subject | TNFSF4 | en_US |
dc.subject | TSLP | en_US |
dc.subject | genetic susceptibility | en_US |
dc.subject | invasive aspergillosis | en_US |
dc.subject | monocytes | en_US |
dc.subject | serum biomarkers | en_US |
dc.title | Polymorphisms 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.type | Article | en_US |
dc.identifier.eissn | 2309-608X | |
dc.contributor.department | CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover. | en_US |
dc.identifier.journal | Journal of fungi (Basel, Switzerland) | en_US |
dc.source.volume | 7 | |
dc.source.issue | 1 | |
refterms.dateFOA | 2021-01-22T12:28:33Z | |
dc.source.journaltitle | Journal of fungi (Basel, Switzerland) | |
dc.source.country | Switzerland |