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, 140 school-age and 131 pre-school children with asthma/wheeze from U-BIOPRED cohort, of whom 595 had severe disease. We applied clustering methods to identify and 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 to 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 amongst 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
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, 140 school-age and 131 pre-school children with asthma/wheeze from U-BIOPRED cohort, of whom 595 had severe disease. We applied clustering methods to identify and 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 to 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 amongst 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
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: 26 Nov 2021 06:56
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Author:
S. Fontanella
Author:
A. Selby
Corporate Author: U-BIOPRED Consortium
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