{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:05:55Z","timestamp":1789927555155,"version":"4.0.1"},"reference-count":94,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"ERA-NET Pathogenomics","award":["PIM2010EPA-00756"],"award-info":[{"award-number":["PIM2010EPA-00756"]}]},{"name":"Fondo de Investigaciones Sanitarias","award":["PI12\/02688"],"award-info":[{"award-number":["PI12\/02688"]}]},{"name":"The Collaborative Research Center\/Transregio 124 FungiNet"},{"name":"Funda\u00e7\u00e3o para a Cincia e Tecnologia, Portugal,","award":["SFRH\/BPD\/96176\/2013"],"award-info":[{"award-number":["SFRH\/BPD\/96176\/2013"]}]},{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the<jats:italic>IL4R<\/jats:italic><jats:sub>rs2107356<\/jats:sub>and<jats:italic>IL8<\/jats:italic><jats:sub>rs2227307<\/jats:sub>SNPs (using dbSNP numbering) were associated with an increased risk of IA (<jats:italic>IL4R<\/jats:italic><jats:sub>rs2107356<\/jats:sub>odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09;<jats:italic>IL8<\/jats:italic><jats:sub>rs2227307<\/jats:sub>OR, 1.73; 95% CI, 1.06 to 2.81), whereas the<jats:italic>IL12B<\/jats:italic><jats:sub>rs3212227<\/jats:sub>and<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705<\/jats:sub>variants were significantly associated with a decreased risk of developing the infection (<jats:italic>IL12B<\/jats:italic><jats:sub>rs3212227<\/jats:sub>OR, 0.60; 95% CI, 0.38 to 0.96;<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705<\/jats:sub>OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the<jats:italic>IL4R<\/jats:italic><jats:sub>rs2107356<\/jats:sub>and<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705<\/jats:sub>SNPs was stronger in allo-HSCT (<jats:italic>IL4R<\/jats:italic><jats:sub>rs2107356<\/jats:sub>OR, 5.63; 95% CI, 1.20 to 3.09;<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705<\/jats:sub>OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly,<jats:italic>in vitro<\/jats:italic>studies revealed that carriers of the<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705C<\/jats:sub>allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (<jats:italic>P<\/jats:italic>= 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFN\u03b3) mRNA (<jats:italic>P<\/jats:italic>= 0.049) and IFN\u03b3 and tumor necrosis factor alpha (TNF-\u03b1) cytokines (<jats:italic>P<\/jats:italic>value for 96 h of treatment with lipopolysaccharide [<jats:italic>P<\/jats:italic><jats:sub>LPS-96 h<\/jats:sub>], 0.057;<jats:italic>P<\/jats:italic>value for 96 h of treatment with phytohemagglutinin [<jats:italic>P<\/jats:italic><jats:sub>PHA-96 h<\/jats:sub>], 0.036;<jats:italic>P<\/jats:italic><jats:sub>LPS+PHA-96 h<\/jats:sub>= 0.030;<jats:italic>P<\/jats:italic><jats:sub>PHA-72 h<\/jats:sub>= 0.045;<jats:italic>P<\/jats:italic><jats:sub>LPS+PHA-72 h<\/jats:sub>= 0.018;<jats:italic>P<\/jats:italic><jats:sub>LPS-96 h<\/jats:sub>= 0.058;<jats:italic>P<\/jats:italic><jats:sub>LPS+PHA-96 h<\/jats:sub>= 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564;<jats:italic>P<\/jats:italic><jats:sub>\u22122 log likehood ratio test<\/jats:sub>= 5.2 \u00b7 10<jats:sup>\u22124<\/jats:sup>and<jats:italic>P<\/jats:italic><jats:sub>50.000 permutation test<\/jats:sub>= 9.34 \u00b7 10<jats:sup>\u22125<\/jats:sup>). These findings suggest that the<jats:italic>IFN<\/jats:italic>\u03b3<jats:sub>rs2069705<\/jats:sub>SNP influences the risk of IA and that predictive models built with<jats:italic>IFN<\/jats:italic>\u03b3,<jats:italic>IL8<\/jats:italic>,<jats:italic>IL12p70<\/jats:italic>, and<jats:italic>VEGFA<\/jats:italic>variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.<\/jats:p>","DOI":"10.1128\/iai.01359-15","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:24:41Z","timestamp":1450153481000},"page":"643-657","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium"],"prefix":"10.1128","volume":"84","author":[{"given":"C. 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