Roberts, Graham; Fontanella, Sara; Selby, Anna; Howard, Rebecca; Filippi, Sarah; Hedlin, Gunilla; Nordlund, Bjorn; Howarth, Peter; Hashimoto, Simone; Brinkman, Peter; Fleming, Louise J; Murray, Clare; Bush, Andrew; Frey, Urs; Singer, Florian; Schoos, Ann-Marie Malby; van Aalderen, Wim; Djukanovic, Ratko; Chung, K Fan; Sterk, Peter J; ... (2020). Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma. Journal of allergy and clinical immunology, 146(4), pp. 821-830. Elsevier 10.1016/j.jaci.2020.02.031
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Connectivity patterns between multiple allergen specific IgE antibodies and their association with severe asthma.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (2MB) | Request a copy |
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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