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Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis

Please always quote using this URN: urn:nbn:de:bvb:20-opus-165386
  • Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of theInvasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.show moreshow less

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Metadaten
Author: Andreas Dix, Kristin Czakai, Jan Springer, Mirjam Fliesser, Michael Bonin, Reinhard Guthke, Anna L. Schmitt, Hermann Einsele, Jörg Linde, Jürgen Löffler
URN:urn:nbn:de:bvb:20-opus-165386
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Frontiers in Microbiology
Year of Completion:2016
Issue:7
Pagenumber:320
Source:Frontiers in Microbiology 2016 7:320. doi: 10.3389/fmicb.2016.00320
DOI:https://doi.org/10.3389/fmicb.2016.00320
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:allogeneic stem cell transplantation; fungal infection; gene expression data; human biomarker; invasive aspergillosis
Release Date:2018/10/21
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International