دورية أكاديمية
أعرض في EDS

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium.

التفاصيل البيبلوغرافية
العنوان: Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium.
المؤلفون: Lupiañez CB; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Canet LM; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Carvalho A; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal., Alcazar-Fuoli L; Mycology Reference Laboratory, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain., Springer J; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Lackner M; Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Segura-Catena J; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Comino A; Experimental Research Unit, Virgen de las Nieves University Hospital, Granada, Spain., Olmedo C; Experimental Research Unit, Virgen de las Nieves University Hospital, Granada, Spain., Ríos R; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Fernández-Montoya A; Blood Transfusion Regional Centre and Sectorial Tissue Bank, Granada, Spain., Cuenca-Estrella M; Mycology Reference Laboratory, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Madrid, Spain., Solano C; Hematology Department, Clinic University Hospital of Valencia, Valencia, Spain., López-Nevot MÁ; Immunology Department, Virgen de las Nieves University Hospital, Granada, Spain., Cunha C; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal., Oliveira-Coelho A; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal., Villaescusa T; Hematology Department, University Hospital of Salamanca, Salamanca, Spain Hematology Department, Jiménez Díaz Foundation, Madrid, Spain., Fianchi L; Istituto di Ematologia, Università Cattolica del S. Cuore, Rome, Italy., Aguado JM; Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain., Pagano L; Istituto di Ematologia, Università Cattolica del S. Cuore, Rome, Italy., López-Fernández E; Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Potenza L; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy., Luppi M; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Policlinico, Modena, Italy., Lass-Flörl C; Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria., Loeffler J; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Einsele H; Universitätsklinikum Würzburg, Medizinische Klinik II, Würzburg, Germany., Vazquez L; Hematology Department, University Hospital of Salamanca, Salamanca, Spain., Jurado M; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain., Sainz J; Genomic Oncology Department, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain juan.sainz@genyo.es.
مؤلفون مشاركون: PCRAGA Study Group
المصدر: Infection and immunity [Infect Immun] 2015 Dec 14; Vol. 84 (3), pp. 643-57. Date of Electronic Publication: 2015 Dec 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Electronic Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington, DC : American Society For Microbiology
Original Publication: [Bethesda, Md.] American Society for Microbiology.
مواضيع طبية MeSH: Genetic Predisposition to Disease* , Polymorphism, Single Nucleotide*, Aspergillosis/*genetics , Aspergillosis/*immunology , Interferon-gamma/*genetics , Interleukin-12 Subunit p40/*genetics , Interleukin-4 Receptor alpha Subunit/*genetics , Interleukin-8/*genetics, Adult ; Aged ; Alleles ; Case-Control Studies ; Female ; Genotype ; Humans ; Immunocompromised Host/genetics ; Interferon-gamma/immunology ; Interleukin-12 Subunit p40/immunology ; Interleukin-4 Receptor alpha Subunit/immunology ; Interleukin-8/immunology ; Male ; Middle Aged
مستخلص: 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 IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 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 IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 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, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 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; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.
(Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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المشرفين على المادة: 0 (IL12B protein, human)
0 (IL4R protein, human)
0 (Interleukin-12 Subunit p40)
0 (Interleukin-4 Receptor alpha Subunit)
0 (Interleukin-8)
82115-62-6 (Interferon-gamma)
تواريخ الأحداث: Date Created: 20151216 Date Completed: 20160829 Latest Revision: 20220408
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4771352
DOI: 10.1128/IAI.01359-15
PMID: 26667837
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-5522
DOI:10.1128/IAI.01359-15