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Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma

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Title: Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma
Authors: Roberts, G
Fontanella, S
Selby, A
Howard, R
Filippi, S
Hedlin, G
Nordlund, B
Howarth, P
Hashimoto, S
Brinkman, P
Fleming, LJ
Murray, C
Bush, A
Frey, U
Singer, F
Schoos, A-MM
Van Aalderen, W
Djukanovic, R
Chung, KF
Sterk, PJ
Adnan, C
U-BIOPRED Consortium
Item Type: Journal Article
Abstract: BACKGROUND: Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. OBJECTIVE: We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. METHODS: IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. RESULTS: Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. CONCLUSIONS: The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.
Issue Date: 1-Oct-2020
Date of Acceptance: 27-Feb-2020
URI: http://hdl.handle.net/10044/1/81403
DOI: 10.1016/j.jaci.2020.02.031
ISSN: 0091-6749
Publisher: Elsevier
Start Page: 821
End Page: 830
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 146
Issue: 4
Copyright Statement: © 2020 American Academy of Allergy, Asthma & Immunology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Asthma
allergic sensitization
cluster
network analysis
PEDIATRIC SEVERE ASTHMA
CLINICAL SYMPTOMS
SENSITIZATION
CHILDHOOD
RESPONSES
Asthma
allergic sensitization
cluster
network analysis
U-BIOPRED Consortium
Asthma
allergic sensitization
cluster
network analysis
1107 Immunology
Allergy
Publication Status: Published
Conference Place: United States
Online Publication Date: 2020-03-15
Appears in Collections:Mathematics
Statistics
National Heart and Lung Institute
Faculty of Medicine
Faculty of Natural Sciences