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

Sanchez-Maldonado JM, Moniz-Diez A, Ter Horst R, Campa D, Cabrera-Serrano AJ, Martinez-Bueno M, Garrido-Collado MDP, Hernandez-Mohedo F, Fernandez-Puerta L, Lopez-Nevot MA, Cunha C, Gonzalez-Sierra PA, Springer J, Lackner M, Alcazar-Fuoli L, Fianchi L, Aguado JM, Pagano L, Lopez-Fernandez E, Clavero E, Potenza L, Luppi M, Moratalla L, Solano C, Sampedro A, Cuenca-Estrella M, Lass-Florl C, Canzian F, Loeffler J, Li Y, Einsele H, Netea MG, Vazquez L, Carvalho A, Jurado M, Sainz J (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 7

Pages Range: 1-17

Article Number: 4

Journal Issue: 1

DOI: 10.3390/jof7010004

Abstract

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.

Involved external institutions

University of Pisa / Università di Pisa (UniPi) Italy (IT) Universidad de Granada Spain (ES) Hospital Universitario Virgen de las Nieves Spain (ES) Universitätsklinikum Würzburg Germany (DE) Medizinische Universität Innsbruck Austria (AT) Radboud University Nijmegen Netherlands (NL) Universidade do Minho Portugal (PT) Catholic University of the Sacred Heart / Università Cattolica del Sacro Cuore Italy (IT) Research Institute Hospital 12 de Octubre (Imas12) Spain (ES) Università degli Studi di Modena e Reggio Emilia (UNIMORE) Italy (IT) Universidad Carlos III de Madrid (UC3M) Spain (ES) University of València / Universitat de València Spain (ES) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Salamanca / Universidad de Salamanca Spain (ES)

How to cite

APA:

Sanchez-Maldonado, J.M., Moniz-Diez, A., Ter Horst, R., Campa, D., Cabrera-Serrano, A.J., Martinez-Bueno, M.,... Sainz, J. (2021). 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. Journal of Fungi, 7(1), 1-17. https://doi.org/10.3390/jof7010004

MLA:

Sanchez-Maldonado, Jose Manuel, et al. "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." Journal of Fungi 7.1 (2021): 1-17.

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