@phdthesis{Etter2024,
  author    = {Etter, Sonja},
  title     = {Einfluss von beruflicher \(Aspergillus\) \(fumigatus\)-Exposition auf die adaptive Immunantwort via ELISpot und Western Blot},
  doi       = {10.25972/OPUS-34858},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-348582},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Bereits in Vorstudien konnte dargelegt werden, dass eine signifikante Korrelation zwischen der T-Zell-Zytokin-Antwort und der berufs- bzw. umweltbedingten Schimmelpilzbelastung besteht. Ziel der vorliegenden Studie war, eine m{\"o}gliche Kombination von Biomarkern ausfindig zu machen, die ver{\"a}nderte T-Zell-Antworten auf A. fumigatus- Antigene bei beruflich Exponierten im Vergleich zu Kontrollprobanden/-innen vorhersagen kann. Um geeignete Marker f{\"u}r das Bio-Monitoring zu finden, wurden zur T-Zell-Aktivierung ein myzeliales A. fumigatus - Lysat und 12 proteinogene Antigene in ELISpot-Versuchen f{\"u}r die Signaturzytokine IFN-γ (TH1), IL-5 (TH2) und IL-17A (TH17) der Haupt-TH-Subpopulationen getestet. Es zeigten sich bei den Biolandwirten/-innen erwartungsgem{\"a}ß erh{\"o}hte TH1- und TH2-Antworten auf die Mehrzahl der verwendeten spezifischen A. fumigatus-Antigene, die m{\"o}glicherweise eine Schimmelpilzbelastung serologisch nachweisbar machen. Insbesondere die spezifischen A. fumigatus-Antigene Aspf22, CatB und CipC konnten eine Trennsch{\"a}rfe zwischen den beiden Kohorten hinsichtlich ihrer IFN-γ- und IL-5-Zytokinantwort erzielen. Unterschiede in der TH17-Antwort aufgrund chronischer beruflicher Sporenbelastung ohne Krankheitskorrelat konnten nicht explizit festgestellt werden. Weiterhin ergab sich, dass erh{\"o}hte TH2-Immunreaktionen, sofern sie mit einer ad{\"a}quaten TH1-gerichteten Immunantwort einhergehen und damit eine ausgeglichene TH2/TH1-Balance besteht, nicht zwangsl{\"a}ufig zu Hypersensitivit{\"a}tserkrankungen f{\"u}hren. Im Vergleich zu Langzeitexponierten wurden teilweise {\"u}berlappende TH-Zellfrequenzen bei beruflich exponierten Biolandwirten/-innen ermittelt. Welche entscheidende Rolle Treg-Zellen bei der Eind{\"a}mmung {\"u}berschießender Immunantworten einnehmen, kann hieraus erahnt werden.},
  subject      = {Schimmelpilzallergie},
  language  = {de}
}
@article{LauruschkatEtterSchnacketal.2021,
  author    = {Lauruschkat, Chris D. and Etter, Sonja and Schnack, Elisabeth and Ebel, Frank and Sch{\"a}uble, Sascha and Page, Lukas and R{\"u}mens, Dana and Dragan, Mariola and Schlegel, Nicolas and Panagiotou, Gianni and Kniemeyer, Olaf and Brakhage, Axel A. and Einsele, Hermann and Wurster, Sebastian and Loeffler, Juergen},
  title     = {Chronic occupational mold exposure drives expansion of Aspergillus-reactive type 1 and type 2 T-helper cell responses},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {9},
  issn      = {2309-608X},
  doi       = {10.3390/jof7090698},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245202},
  year      = {2021},
  abstract  = {Occupational mold exposure can lead to Aspergillus-associated allergic diseases including asthma and hypersensitivity pneumonitis. Elevated IL-17 levels or disbalanced T-helper (Th) cell expansion were previously linked to Aspergillus-associated allergic diseases, whereas alterations to the Th cell repertoire in healthy occupationally exposed subjects are scarcely studied. Therefore, we employed functional immunoassays to compare Th cell responses to A. fumigatus antigens in organic farmers, a cohort frequently exposed to environmental molds, and non-occupationally exposed controls. Organic farmers harbored significantly higher A. fumigatus-specific Th-cell frequencies than controls, with comparable expansion of Th1- and Th2-cell frequencies but only slightly elevated Th17-cell frequencies. Accordingly, Aspergillus antigen-induced Th1 and Th2 cytokine levels were strongly elevated, whereas induction of IL-17A was minimal. Additionally, increased levels of some innate immune cell-derived cytokines were found in samples from organic farmers. Antigen-induced cytokine release combined with Aspergillus-specific Th-cell frequencies resulted in high classification accuracy between organic farmers and controls. Aspf22, CatB, and CipC elicited the strongest differences in Th1 and Th2 responses between the two cohorts, suggesting these antigens as potential candidates for future bio-effect monitoring approaches. Overall, we found that occupationally exposed agricultural workers display a largely balanced co-expansion of Th1 and Th2 immunity with only minor changes in Th17 responses.},
  language  = {en}
}
@article{LauruschkatPageWhiteetal.2021,
  author    = {Lauruschkat, Chris D. and Page, Lukas and White, P. Lewis and Etter, Sonja and Davies, Helen E. and Duckers, Jamie and Ebel, Frank and Schnack, Elisabeth and Backx, Matthijs and Dragan, Mariola and Schlegel, Nicolas and Kniemeyer, Olaf and Brakhage, Axel A. and Einsele, Hermann and Loeffler, Juergen and Wurster, Sebastian},
  title     = {Development of a simple and robust whole blood assay with dual co-stimulation to quantify the release of T-cellular signature cytokines in response to Aspergillus fumigatus antigens},
  series = {Journal of Fungi},
  volume    = {7},
  journal   = {Journal of Fungi},
  number    = {6},
  issn      = {2309-608X},
  doi       = {10.3390/jof7060462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241025},
  year      = {2021},
  abstract  = {Deeper understanding of mold-induced cytokine signatures could promote advances in the diagnosis and treatment of invasive mycoses and mold-associated hypersensitivity syndromes. Currently, most T-cellular immunoassays in medical mycology require the isolation of mononuclear cells and have limited robustness and practicability, hampering their broader applicability in clinical practice. Therefore, we developed a simple, cost-efficient whole blood (WB) assay with dual α-CD28 and α-CD49d co-stimulation to quantify cytokine secretion in response to Aspergillus fumigatus antigens. Dual co-stimulation strongly enhanced A. fumigatus-induced release of T-cellular signature cytokines detectable by enzyme-linked immunosorbent assay (ELISA) or a multiplex cytokine assay. Furthermore, T-cell-dependent activation and cytokine response of innate immune cells was captured by the assay. The protocol consistently showed little technical variation and high robustness to pre-analytic delays of up to 8 h. Stimulation with an A. fumigatus lysate elicited at least 7-fold greater median concentrations of key T-helper cell signature cytokines, including IL-17 and the type 2 T-helper cell cytokines IL-4 and IL-5 in WB samples from patients with Aspergillus-associated lung pathologies versus patients with non-mold-related lung diseases, suggesting high discriminatory power of the assay. These results position WB-ELISA with dual co-stimulation as a simple, accurate, and robust immunoassay for translational applications, encouraging further evaluation as a platform to monitor host immunity to opportunistic pathogens.},
  language  = {en}
}