Cargando…

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

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 ascer...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, Canzian, Federico, Loeffler, Juergen, Li, Yang, Einsele, Hermann, Netea, Mihai G., Vázquez, Lourdes, Carvalho, Agostinho, Jurado, Manuel, Sainz, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823601/
https://www.ncbi.nlm.nih.gov/pubmed/33374839
http://dx.doi.org/10.3390/jof7010004
Descripción
Sumario: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.