RT Journal Article
T1 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.
A1 Sanchez-Maldonado, Jose Manuel
A1 Moñiz-Diez, Ana
A1 Ter Horst, Rob
A1 Campa, Daniele
A1 Cabrera-Serrano, Antonio Jose
A1 Martinez-Bueno, Manuel
A1 Garrido-Collado, Maria Del Pilar
A1 Hernandez-Mohedo, Francisca
A1 Fernandez-Puerta, Laura
A1 Lopez-Nevot, Miguel Angel
A1 Cunha, Cristina
A1 Gonzalez-Sierra, Pedro Antonio
A1 Springer, Jan
A1 Lackner, Michaela
A1 Alcazar-Fuoli, Laura
A1 Fianchi, Luana
A1 Aguado, Jose Maria
A1 Pagano, Livio
A1 Lopez-Fernandez, Elisa
A1 Clavero, Esther
A1 Potenza, Leonardo
A1 Luppi, Mario
A1 Moratalla, Lucia
A1 Solano, Carlos
A1 Sampedro, Antonio
A1 Cuenca-Estrella, Manuel
A1 Lass-Flörl, Cornelia
A1 Pcraga Study Group, 
A1 Canzian, Federico
A1 Loeffler, Juergen
A1 Li, Yang
A1 Einsele, Hermann
A1 Netea, Mihai G
A1 Vazquez, Lourdes
A1 Carvalho, Agostinho
A1 Jurado, Manuel
A1 Sainz, Juan
K1 B cells
K1 MAPKAPK2
K1 TNFSF14
K1 TNFSF4
K1 TSLP
K1 genetic susceptibility
K1 invasive aspergillosis
K1 monocytes
K1 serum biomarkers
AB 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.
PB MDPI AG
YR 2020
FD 2020-12-23
LK http://hdl.handle.net/10668/16867
UL http://hdl.handle.net/10668/16867
LA en
NO Sánchez-Maldonado JM, Moñiz-Díez A, Ter Horst R, Campa D, Cabrera-Serrano AJ, Martínez-Bueno M, et al. 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. J Fungi (Basel). 2020 Dec 23;7(1):4.
NO This study was supported by grants PI20/01845, PI12/02688, and ISCIII-FEDER PI17/02276from Fondo de Investigaciones Sanitarias (Madrid, Spain), PIM2010EPA-00756 from the ERA-NETPathoGenoMics (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 researchand innovation programme under grant agreement no. 847507, and the “la Caixa” Foundation(ID 100010434) and FCT under the agreement LCF/PR/HP17/52190003).
DS RISalud
RD Apr 4, 2025