rAsp f3 and rAsp f4 are associated with bronchiectasis in allergic fungal airways disease

Woolnough, Kerry; Craner, Michelle; Pashley, Catherine H.; Wardlaw, Andrew J.

doi:10.1016/j.anai.2017.10.026

Cited by 4 publications

(6 citation statements)

References 8 publications

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“…Asp f3 and f4 which were associated with bronchiectasis were not associated with impairment in lung function. 49 FAO in AFAD is presumably caused by pathology in the small airways, although the inflammatory profile appears distinct from smoking-related COPD, a condition which many patients with AFAD are labelled as having when FAO is prominent. 81 Eosinophils are potent inducers of fibrotic reactions, and it is this pathway that might be responsible both for AFAD-associated fixed airflow obstruction and lung fibrosis, with IgE sensitisation acting as a marker of eosinophil production and activation rather than directly causing the pathology.…”

Section: Pathogenesis Of Afadmentioning

confidence: 99%

“… 47 , 48 We found that of the five recombinant allergens of A. fumigatus mentioned above, Asp f3 and f4 were the most closely associated with bronchiectasis in patients with AFAD (none of the allergens were associated with fixed airflow obstruction (FAO)). 49 Identification and detailed characterisation of fungal allergens are complex, difficult and time-consuming. While 23 allergens of A. fumigatus are listed on the WHO website and 81 were identified using phage display, relatively few have been fully characterised.…”

Section: Fungal Allergensmentioning

confidence: 99%

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New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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Allergy to airway-colonising, thermotolerant, filamentous fungi represents a distinct eosinophilic endotype of often severe lung disease. This endotype, which particularly affects adult asthma, but also complicates other airway diseases and sometimes occurs de novo, has a heterogeneous presentation ranging from severe eosinophilic asthma to lobar collapse. Its hallmark is lung damage, characterised by fixed airflow obstruction (FAO), bronchiectasis and lung fibrosis. It has a number of monikers including severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis/mycosis (ABPA/ M), but these exclusive terms constitute only sub-sets of the condition. In order to capture the full extent of the syndrome we prefer the inclusive term allergic fungal airway disease (AFAD), the criteria for which are IgE sensitisation to relevant fungi in association with airway disease. The primary fungus involved is Aspergillus fumigatus, but a number of other thermotolerant species from several genera have been implicated. The unifying mechanism involves germination of inhaled fungal spores in the lung in the context of IgE sensitisation, leading to a persistent and vigorous eosinophilic inflammatory response in association with release of fungal proteases. Most allergenic fungi, including Alternaria and Cladosporium species, are not thermotolerant and cannot germinate in the airways so only act as aeroallergens and do not cause AFAD. Studies of the airway mycobiome have shown that A. fumigatus colonises the normal as much as the asthmatic airway, suggesting it is the tendency to become IgE-sensitised that is the critical triggering factor for AFAD rather than colonisation per se. Treatment is aimed at preventing exacerbations with glucocorticoids and increasingly by the use of anti-T2 biological therapies. Anti-fungal therapy has a limited place in management, but is an effective treatment for fungal bronchitis which complicates AFAD in about 10% of cases.

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Section: Pathogenesis Of Afadmentioning

confidence: 99%

Section: Fungal Allergensmentioning

confidence: 99%

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Wardlaw¹,

Rick²,

Özyiğit³

et al. 2021

JAA

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“…However, only five allergens of A. fumigatus are commercially available. Despite the limited panel, we demonstrated that IgE sensitization to Asp f 3 and f 4 was closely related to the likelihood of developing bronchiectasis in patients with AFAD 10 . There is limited information on the relationship between clinical outcomes and IgE sensitization to the other 18 A. fumigatus allergens described by the WHO/IUIS 11 .…”

Section: Introductionmentioning

confidence: 78%

“…Despite the limited panel, we demonstrated that IgE sensitization to Asp f 3 and f 4 was closely related to the likelihood of developing bronchiectasis in patients with AFAD. 10 There is limited information on the relationship between clinical outcomes and IgE sensitization to the other 18 A. fumigatus allergens described by the WHO/IUIS. 11 Phage display was suggestive that many more allergens of A. fumigatus remain to be characterized.…”

Section: Introductionmentioning

confidence: 99%

Identification of allergens from Aspergillus fumigatus—Potential association with lung damage in asthma

Rick,

Woolnough,

Richardson

et al. 2024

Allergy

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BackgroundComponent‐resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1‐ or 2‐dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained.MethodsWe used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti‐human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract.ResultsOf the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus‐sensitized people with asthma, 23 non‐fungal‐sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose‐bisphosphate aldolase class II (FBA2) (33%), NAD‐dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens.ConclusionIn conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.

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“…In COPD, rAsp f 1 and 3 appear to associate with bronchiectasis–COPD overlap while rAsp f 1, 15 and 17 are related to very frequent exacerbations ( i.e. three or more COPD exacerbations annually) [ 1 , 46 , 50 ]. However, these prior works in COPD, while demonstrating clinical relevance, only include a small, restricted and select number of rAsp f allergens for evaluation, necessitating a broader understanding of their use and relevance in clinical COPD.…”

Section: Discussionmentioning

confidence: 99%

Sensitisation to recombinantAspergillus fumigatusallergens and clinical outcomes in COPD

et al. 2022

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BackgroundVariable clinical outcomes are reported with fungal sensitisation in COPD, and it remains unclear which fungi and what allergens associate with poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown.MethodsA prospective multicenter assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia, and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and Topological Data Analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation sub-groups exist and their related clinical outcomes.ResultsAspergillus fumigatus sensitisation associates with increased exacerbations in COPD. Unsupervised cluster analyses reveal two “fungal sensitisation” groups, one characterized by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group confers even poorer outcome. The second group, characterized by Cladosporium sensitisation is more symptomatic. Significant numbers of individuals demonstrate sensitisation responses to only recombinant (as opposed to crude) Aspergillus fumigatus allergens 1, 3, 5, and 6, and exhibit higher exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a sub-group within “Aspergillus sensitised COPD” enriched for frequent exacerbators.ConclusionAspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remain overlooked by assessment of only crude Aspergillus allergens.

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rAsp f3 and rAsp f4 are associated with bronchiectasis in allergic fungal airways disease

Cited by 4 publications

References 8 publications

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

New Perspectives in the Diagnosis and Management of Allergic Fungal Airway Disease

Identification of allergens from Aspergillus fumigatus—Potential association with lung damage in asthma

Sensitisation to recombinantAspergillus fumigatusallergens and clinical outcomes in COPD

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