title: Proteomic Profiling of Serological Responses to Aspergillus fumigatus Antigens in Patients with Invasive Aspergillosis.
abstract: Aspergillus fumigatus is the species that most commonly causes the opportunistic infection invasive aspergillosis (IA) in patients being treated for hematological malignancies. Little is known about the A. fumigatus proteins that trigger the production of Aspergillus-specific IgG antibodies during the course of IA. To characterize the serological response to A. fumigatus protein antigens, mycelial proteins were separated by 2-D gel electrophoresis. The gels were immunoblotted with sera from patients with probable and proven IA and control patients without IA. We identified 49 different fungal proteins, which gave a positive IgG antibody signal. Most of these antigens play a role in primary metabolism and stress responses. Overall, our analysis identified 18 novel protein antigens from A. fumigatus. To determine whether these antigens can be used as diagnostic or prognostic markers or exhibit a protective activity, we employed supervised machine learning with decision trees. We identified two candidates for further analysis, the protein antigens CpcB and Shm2. Heterologously produced Shm2 induced a strongly proinflammatory response in human peripheral blood mononuclear cells after in vitro stimulation. In contrast, CpcB did not activate the immune response of PBMCs. These findings could serve as the basis for the development of an immunotherapy of IA.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.|Institute of Microbiology, Friedrich Schiller University , 07743 Jena, Germany.
authors.forename: Janka
authors.initials: J
authors.lastname: Teutschbein
authors.affiliation: Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Simon
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lother
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Springer
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.|Institute of Microbiology, Friedrich Schiller University , 07743 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.affiliation: Department of Clinical Microbiology, Trinity College Dublin , Dublin 2, Ireland.
authors.forename: C Oliver
authors.initials: CO
authors.lastname: Morton
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Löffler
authors.affiliation: Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Department of Haematology, St. James's Hospital , Dublin 8, Ireland.
authors.forename: Eibhlin
authors.initials: E
authors.lastname: Conneally
authors.affiliation: Department of Clinical Microbiology, Trinity College Dublin , Dublin 2, Ireland.|Department of Haematology, St. James's Hospital , Dublin 8, Ireland.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Rogers
authors.affiliation: Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.|Institute of Microbiology, Friedrich Schiller University , 07743 Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany.|Institute of Microbiology, Friedrich Schiller University , 07743 Jena, Germany.|Integrated Research and Treatment Center, Center for Sepsis Control and Care Jena (CSCC), University Hospital , 07747 Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
mesh_terms: D000946:Antigens, Fungal / Q000032:analysis*; D001228:Aspergillosis / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005656:Fungal Proteins / Q000032:analysis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology; D040901:Proteomics / Q000379:methods*; D000069553:Supervised Machine Learning
chemical_list: D000946:Antigens, Fungal; D005656:Fungal Proteins; D007074:Immunoglobulin G
keywords: Aspergillus fumigatus; decision trees; immunoproteomics; invasive aspergillosis; protein antigens