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Lemonnier, N.* ; Melén, E.* ; Jiang, Y.* ; Joly, S.* ; Ménard, C.* ; Aguilar, D.* ; Acosta-Perez, E.* ; Bergström, A.* ; Boutaoui, N.* ; Bustamante, M.* ; Canino, G.* ; Forno, E.* ; González, J.R.* ; Garcia-Aymerich, J.* ; Gruzieva, O.* ; Guerra, S.* ; Heinrich, J. ; Kull, I.* ; Maurolagoitia, J.I.* ; Rodriguez, L.S.* ; Thiering, E. ; Wickman, M.* ; Akdis, C.* ; Akdis, M.* ; Chen, W.* ; Keil, T.* ; Koppelman, G.H.* ; Siroux, V.* ; Xu, C.J.* ; Hainaut, P.* ; Standl, M. ; Sunyer, J.* ; Celedón, J.C.* ; Antó, J.M.* ; Bousquet, J.*

A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents.

Allergy 75, 3248-3260 (2020)

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Background Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Asthma ; Atopic Dermatitis ; Multimorbidity ; Rhinitis ; Transcriptomics; Childhood Asthma; Eczema; Medall; Alpha; Mechanisms; Disease; Impact; Rna

ISSN (print) / ISBN 0105-4538

e-ISSN 1398-9995

Journal Allergy

Quellenangaben Volume: 75, Issue: 12, Pages: 3248-3260

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology (EPI)