Proteomic Profiling of Serological Responses to Aspergillus fumigatus Antigens in Patients with Invasive Aspergillosis.

Autor:	Teutschbein J; 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., Simon S; Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany., Lother J; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany., Springer J; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany., Hortschansky P; 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., Morton CO; Department of Clinical Microbiology, Trinity College Dublin , Dublin 2, Ireland., Löffler J; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany., Einsele H; Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg , 97080 Würzburg, Germany., Conneally E; Department of Haematology, St. James's Hospital , Dublin 8, Ireland., Rogers TR; Department of Clinical Microbiology, Trinity College Dublin , Dublin 2, Ireland.; Department of Haematology, St. James's Hospital , Dublin 8, Ireland., Guthke R; Research Group Systems Biology/Bioinformatics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI) , 07745 Jena, Germany., Brakhage AA; 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., Kniemeyer O; 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.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2016 May 06; Vol. 15 (5), pp. 1580-91. Date of Electronic Publication: 2016 Mar 24.
DOI:	10.1021/acs.jproteome.6b00042
Abstrakt:	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.
Databáze:	MEDLINE
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