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


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
10 2020
Historique:
received: 06 05 2019
revised: 23 02 2020
accepted: 27 02 2020
pubmed: 20 3 2020
medline: 16 3 2021
entrez: 20 3 2020
Statut: ppublish

Résumé

Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. 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. 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. The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma.

Sections du résumé

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.

Identifiants

pubmed: 32188567
pii: S0091-6749(20)30341-9
doi: 10.1016/j.jaci.2020.02.031
pii:
doi:

Substances chimiques

Allergens 0
Biomarkers 0
Immunoglobulin E 37341-29-0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

821-830

Subventions

Organisme : Medical Research Council
ID : MR/S025340/1
Pays : United Kingdom

Informations de copyright

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Graham Roberts (G)

Clinical and Experimental Sciences and Human Development in Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Newport, Isle of Wight, United Kingdom. Electronic address: g.c.roberts@soton.ac.uk.

Sara Fontanella (S)

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Anna Selby (A)

Clinical and Experimental Sciences and Human Development in Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom.

Rebecca Howard (R)

Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.

Sarah Filippi (S)

Department of Mathematics, Imperial College London, London, United Kingdom.

Gunilla Hedlin (G)

Department of Women's and Children's Health and the Centre for Allergy Research, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.

Bjorn Nordlund (B)

Department of Women's and Children's Health and the Centre for Allergy Research, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.

Peter Howarth (P)

Clinical and Experimental Sciences and Human Development in Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

Simone Hashimoto (S)

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Peter Brinkman (P)

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Louise J Fleming (LJ)

National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom.

Clare Murray (C)

Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.

Andrew Bush (A)

Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom; COPSAC (Copenhagen Prospective Studies on Asthma I Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Urs Frey (U)

University Children's Hospital Basel UKBB, University of Basel, Spitalstrasse, Basel, Switzerland.

Florian Singer (F)

Division of Respiratory Medicine, Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland.

Ann-Marie Malby Schoos (AM)

COPSAC (Copenhagen Prospective Studies on Asthma I Childhood), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.

Wim van Aalderen (W)

Department of Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Ratko Djukanovic (R)

Clinical and Experimental Sciences and Human Development in Health Academic Unit, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

K Fan Chung (KF)

Department of Respiratory Paediatrics, Royal Brompton Hospital, London, United Kingdom.

Peter J Sterk (PJ)

Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Custovic Adnan (C)

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

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