TY  - JOUR
A1  - Sánchez-Maldonado, Jose Manuel
A1  - Moñiz-Díez, Ana
A1  - ter Horst, Rob
A1  - Campa, Daniele
A1  - Cabrera-Serrano, Antonio José
A1  - Martínez-Bueno, Manuel
A1  - Garrido-Collado, María del Pilar
A1  - Hernández-Mohedo, Francisca
A1  - Fernández-Puerta, Laura
A1  - López-Nevot, Miguel Ángel
A1  - Cunha, Cristina
A1  - González-Sierra, Pedro Antonio
A1  - Springer, Jan
A1  - Lackner, Michaela
A1  - Alcazar-Fuoli, Laura
A1  - Fianchi, Luana
A1  - Aguado, José María
A1  - Pagano, Livio
A1  - López-Fernández, 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  - Canzian, Federico
A1  - Loeffler, Juergen
A1  - Li, Yang
A1  - Einsele, Hermann
A1  - Netea, Mihai G.
A1  - Vázquez, Lourdes
A1  - Carvalho, Agostinho
A1  - Jurado, Manuel
A1  - Sainz, Juan
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
T2  - Journal of Fungi
N2  - 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 TNFSF4\(_{rs7526628T/T}\) genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4\(_{rs7526628T}\) 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 MAPKAPK2\(_{rs12137965G}\) allele increased the risk of IA by 60% (p = 0.0017), whereas each copy of the MAPKAPK2\(_{rs17013271T}\) allele was estimated to decrease the risk of developing the disease (p = 0.0029). Mechanistically, we found that carriers of the risk MAPKAPK2\(_{rs12137965G}\) 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 MAPKAPK2\(_{rs17013271T}\) 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.
KW  - invasive aspergillosis
KW  - TNFSF4
KW  - MAPKAPK2
KW  - genetic susceptibility
KW  - B cells
KW  - monocytes
KW  - serum biomarkers
KW  - TSLP
KW  - TNFSF14
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/22010
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-220107
SN  - 2309-608X
VL  - 7
IS  - 1
ER  -