Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma - 05/10/20
, Sara Fontanella, PhD d, ∗, Anna Selby, DM a, Rebecca Howard, PhD e, Sarah Filippi, PhD f, Gunilla Hedlin, PhD g, Bjorn Nordlund, PhD g, Peter Howarth, DM a, b, Simone Hashimoto, PhD h, i, Peter Brinkman, MSc h, Louise J. Fleming, MD d, j, Clare Murray, MD k, Andrew Bush, MD j, l, Urs Frey, PhD m, Florian Singer, PhD n, Ann-Marie Malby Schoos, MD, PhD l, Wim van Aalderen, PhD i, Ratko Djukanovic, DM a, b, K. Fan Chung, DSc j, Peter J. Sterk, PhD h, Custovic Adnan, MD, PhD, FAAAI don behalf of the
U-BIOPRED Consortium‡
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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, allergic sensitization, cluster, network analysis
Abbreviations used : CRD, c-sIgE, HDM, ISU, JDINAC, SPT, U-BIOPRED
Plan
| U-BIOPRED is supported through an Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement number 115010, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in kind contribution (www.imi.europa.eu). The IMI-funded European Translational Information & Knowledge Management Services (eTRIKS) project (European Union grant code no. 115446) also provided help. |
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| Disclosure of potential conflicts of interest: G. Robert’s University has received honoraria from Thermo Fisher for a sponsored symposium. A.-M. M. Schoos has received a travel grant from Thermo Fisher in the last 3 years. A. Custovic reports personal fees from Thermo Fisher, during the conduct of the study; and personal fees from Novartis, Regeneron, Philips, and Sanofi, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 146 - N° 4
P. 821-830 - octobre 2020 Retour au numéro
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