Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma
Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma
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.
Asthma, allergic sensitization, cluster, network analysis
821-830
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Fontanella, S.
ffb87354-534d-43da-829d-cfba6d0db6ca
Selby, A.
e1464a92-b6b5-47f3-869d-427c575f9da8
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
October 2020
Roberts, Graham
ea00db4e-84e7-4b39-8273-9b71dbd7e2f3
Fontanella, S.
ffb87354-534d-43da-829d-cfba6d0db6ca
Selby, A.
e1464a92-b6b5-47f3-869d-427c575f9da8
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
U-BIOPRED Consortium
(2020)
Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma.
Journal of Allergy and Clinical Immunology, 146 (4), .
(doi:10.1016/j.jaci.2020.02.031).
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.
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Accepted/In Press date: 20 February 2020
e-pub ahead of print date: 15 March 2020
Published date: October 2020
Additional Information:
Funding Information:
This article is presented on behalf of the U-BIOPRED Study Group with input from the U-BIOPRED Patient Input Platform, Ethics Board, and Safety Management Board. We thank Tom Cull who undertook the ImmunoCAP Immuno-Solid phase Allergy Chip assays at University Hospital Southampton NHS Foundation Trust. We also acknowledge help in data and knowledge management from the eTRIKS project, which is funded by the Innovative Medicines Initiative. In addition, we acknowledge the support of the University Hospital Southampton NHS Foundation Trust and the NIHR-Wellcome Trust Clinical Research Facility, Southampton, UK.
Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology
Keywords:
Asthma, allergic sensitization, cluster, network analysis
Identifiers
Local EPrints ID: 438404
URI: http://eprints.soton.ac.uk/id/eprint/438404
ISSN: 0091-6749
PURE UUID: a24d82e7-24c3-42d1-aea8-900dbe361fb4
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Date deposited: 09 Mar 2020 17:32
Last modified: 17 Mar 2024 05:23
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Author:
S. Fontanella
Author:
A. Selby
Corporate Author: U-BIOPRED Consortium
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