| Autor: |
Jose Manuel Sánchez-Maldonado, Ana Moñiz-Díez, Rob ter Horst, Daniele Campa, Antonio José Cabrera-Serrano, Manuel Martínez-Bueno, María del Pilar Garrido-Collado, Francisca Hernández-Mohedo, Laura Fernández-Puerta, Miguel Ángel López-Nevot, Cristina Cunha, Pedro Antonio González-Sierra, Jan Springer, Michaela Lackner, Laura Alcazar-Fuoli, Luana Fianchi, José María Aguado, Livio Pagano, Elisa López-Fernández, Esther Clavero, Leonardo Potenza, Mario Luppi, Lucia Moratalla, Carlos Solano, Antonio Sampedro, Manuel Cuenca-Estrella, Cornelia Lass-Flörl, PCRAGA Study Group, Federico Canzian, Juergen Loeffler, Yang Li, Hermann Einsele, Mihai G. Netea, Lourdes Vázquez, Agostinho Carvalho, Manuel Jurado, Juan Sainz |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Journal of Fungi, Vol 7, Iss 1, p 4 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2309-608X |
| DOI: |
10.3390/jof7010004 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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