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...

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Detalhes bibliográficos
Autores: Sanchez-Maldonado, Jose Manuel, Moniz-Diez, Ana, Ter Horst, Rob, Campa, Daniele, Cabrera-Serrano, Antonio Jose, Martinez-Bueno, Manuel, Garrido-Collado, Maria Del Pilar, Hernandez-Mohedo, Francisca, Fernandez-Puerta, Laura, Lopez-Nevot, Miguel Angel, Cunha, Cristina, Gonzalez-Sierra, Pedro Antonio, Springer, Jan, Lackner, Michaela, Alcazar-Fuoli, Laura, Fianchi, Luana, Aguado, Jose Maria, Pagano, Livio, Lopez-Fernandez, Elisa, Clavero, Esther, Potenza, Leonardo, Luppi, Mario, Moratalla, Lucia, Solano, Carlos, Sampedro, Antonio, Cuenca-Estrella, Manuel, Lass-Florl, Cornelia, Pcraga Study Group, Canzian, Federico, Loeffler, Juergen, Li, Yang, Einsele, Hermann, Netea, Mihai G, Vazquez, Lourdes, Carvalho, Agostinho, Jurado, Manuel, Sainz, Juan
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p15395
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/15395
Access Level:acceso abierto
Palavra-chave:invasive aspergillosis
TNFSF4
MAPKAPK2
genetic susceptibility
B cells
monocytes
serum biomarkers
TSLP
TNFSF14
Descrição
Resumo: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.

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