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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
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
0091-6749
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
U-BIOPRED Consortium
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), 821-830. (doi:10.1016/j.jaci.2020.02.031).

Record type: 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, 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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More information

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
ORCID for Graham Roberts: ORCID iD orcid.org/0000-0003-2252-1248
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 09 Mar 2020 17:32
Last modified: 26 Nov 2021 06:56

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Contributors

Author: Graham Roberts ORCID iD
Author: S. Fontanella
Author: A. Selby
Author: Peter Howarth
Corporate Author: U-BIOPRED Consortium

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