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https://hdl.handle.net/1822/74321
Título: | 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 |
Autor(es): | Sánchez-Maldonado, Jose Manuel Moñiz-Díez, Ana ter Horst, Rob Campa, Daniele Cabrera-Serrano, Antonio José Martínez-Bueno, Manuel Garrido-Collado, María del Pilar Hernández-Mohedo, Francisca Fernández-Puerta, Laura López-Nevot, Miguel Ángel Cunha, Cristina González-Sierra, Pedro Antonio Springer, Jan Lackner, Michaela Alcazar-Fuoli, Laura Fianchi, Luana Aguado, José María Pagano, Livio López-Fernández, Elisa Clavero, Esther Potenza, Leonardo Luppi, Mario Moratalla, Lucia Solano, Carlos Sampedro, Antonio Cuenca-Estrella, Manuel Lass-Flörl, Cornelia PCRAGA Study Group, Canzian, Federico Loeffler, Juergen Li, Yang Einsele, Hermann Netea, Mihai G. Vázquez, Lourdes Carvalho, Agostinho Jurado, Manuel Sainz, Juan |
Palavras-chave: | invasive aspergillosis TNFSF4 MAPKAPK2 genetic susceptibility B cells monocytes serum biomarkers TSLP TNFSF14 |
Data: | 2021 |
Editora: | Multidisciplinary Digital Publishing Institute |
Revista: | Journal of Fungi |
Citação: | Sánchez-Maldonado, J.M.; Moñiz-Díez, A.; ter Horst, R.; Campa, D.; Cabrera-Serrano, A.J.; Martínez-Bueno, M.; Garrido-Collado, M.d.P.; Hernández-Mohedo, F.; Fernández-Puerta, L.; López-Nevot, M.Á.; Cunha, C.; González-Sierra, P.A.; Springer, J.; Lackner, M.; Alcazar-Fuoli, L.; Fianchi, L.; Aguado, J.M.; Pagano, L.; López-Fernández, E.; Clavero, E.; Potenza, L.; Luppi, M.; Moratalla, L.; Solano, C.; Sampedro, A.; Cuenca-Estrella, M.; Lass-Flörl, C.; PCRAGA Study Group; Canzian, F.; Loeffler, J.; Li, Y.; Einsele, H.; Netea, M.G.; Vázquez, L.; Carvalho, A.; Jurado, M.; Sainz, J. 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 2021, 7, 4. https://doi.org/10.3390/jof7010004 |
Resumo(s): | Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the <i>TNFSF4</i> and <i>MAPKAPK2</i> 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 <i>TNFSF4</i><sub>rs7526628T/T</sub> genotype had a significantly increased risk of developing IA (<i>p</i> = 0.00022). We also found that carriers of the <i>TNFSF4</i><sub>rs7526628T</sub> allele showed decreased serum levels of TNFSF14 protein (<i>p</i> = 0.0027), and that their macrophages had a decreased fungicidal activity (<i>p</i> = 0.048). In addition, we observed that each copy of the <i>MAPKAPK2</i><sub>rs12137965G</sub> allele increased the risk of IA by 60% (<i>p</i> = 0.0017), whereas each copy of the <i>MAPKAPK2</i><sub>rs17013271T</sub> allele was estimated to decrease the risk of developing the disease (<i>p</i> = 0.0029). Mechanistically, we found that carriers of the risk <i>MAPKAPK2</i><sub>rs12137965G</sub> allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (<i>p</i> = 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (<i>p</i> = 0.00097). Finally, we also found that carriers of the protective <i>MAPKAPK2</i><sub>rs17013271T</sub> allele had decreased numbers of CD27-IgM-IgD- B cells (<i>p</i> = 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (<i>p</i> = 0.00018 and 0.00023). Altogether, these results suggest a role of the <i>TNFSF4 and MAPKAPK2</i> genes in determining IA risk. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/74321 |
DOI: | 10.3390/jof7010004 |
ISSN: | 2309-608X |
Versão da editora: | https://www.mdpi.com/2309-608X/7/1/4 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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jof-07-00004-v4.pdf | 1,35 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons