2019RICKEMPhD.pdf (5.29 MB)
Fungi In Asthma - Investigation Of The Lung Mycobiome And Characterisation Of Allergens
thesisposted on 2019-07-16, 14:50 authored by Eva-Maria Rick
Asthma is a heterogeneous and complex disease, where sensitisation to, and colonisation with fungi have been associated with decreased lung function. The full spectrum of fungi involved with asthma and their role has not been established due in part to limitations in traditional culture methods. Furthermore, most fungi lack commercially available allergy tests and their allergens have not been characterised. To obtain a better understanding of the fungi involved in asthma, subjects with or without fungal sensitisation provided sputum samples which were subjected to amplicon-based high-throughput sequencing to assess the fungal microbiome (mycobiome). A subset also underwent a bronchoscopy. Fungal sensitised people with asthma showed higher levels of Candida dubliniensis in sputum than non-fungal sensitised asthmatics and healthy controls. Aspergillus tubingensis and Cryptococcus pseudolongus were more prevalent and abundant in bronchoscopy-derived samples, particularly from subjects with asthma, and were significantly associated with decreased sputum neutrophil counts. These fungi could contribute to the asthma phenotype, however, their allergen profile is unknown. This was addressed for A. tubingensis, the IgE response of A. tubingensis and its close relative A. niger were investigated. Only subjects with high A. fumigatus-specific IgE levels (> 17 kU/L) showed sensitisation to these fungi. Yet undescribed IgE cross-reactions with Aspergillus fumigatus proteins Asp f 3 and 6 could be detected, which may contribute to lung inflammation. Other potential IgE cross-reactive allergens were identified using immunoprecipitation of fungal proteins from crude extract. Both known and yet undescribed allergens from A. fumigatus could be detected by these proof-of-principle experiments.
Supervisor(s)Pashley, Catherine; Wardlaw, Andy
Date of award2019-06-07
Author affiliationDepartment of Infection, Immunity and Inflammation
Awarding institutionUniversity of Leicester