Proteomic Profiling of Serological Responses to <i>Aspergillus fumigatus</i> Antigens in Patients with Invasive Aspergillosis

<i>Aspergillus fumigatus</i> 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 <i>A. fumigatus</i> proteins that trigger the production of <i>Aspergillus</i>-specific IgG antibodies during the course of IA. To characterize the serological response to <i>A. fumigatus</i> 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 <i>A. fumigatus</i>. 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 <i>in vitro</i> 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