Understanding allergic multimorbidity within the non-eosinophilic interactome

Autoři: Daniel Aguilar aff001;  Nathanael Lemonnier aff004;  Gerard H. Koppelman aff005;  Erik Melén aff007;  Baldo Oliva aff008;  Mariona Pinart aff002;  Stefano Guerra aff002;  Jean Bousquet aff010;  Josep M. Antó aff002
Působiště autorů: Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Barcelona, Spain aff001;  ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain aff002;  6AM Data Mining, Barcelona, Spain aff003;  Institute for Advanced Biosciences, Inserm U 1209 CNRS UMR 5309 Université Grenoble Alpes, Site Santé, Allée des Alpes, La Tronche, France aff004;  University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen, Netherlands aff005;  University of Groningen, University Medical Center Groningen, GRIAC Research Institute aff006;  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden aff007;  Structural Bioinformatics Group, Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain aff008;  Asthma and Airway Disease Research Center, University of Arizona, Tucson, Arizona, United States of America aff009;  Hopital Arnaud de Villeneuve University Hospital, Montpellier, France aff010;  Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany aff011
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224448



The mechanisms explaining multimorbidity between asthma, dermatitis and rhinitis (allergic multimorbidity) are not well known. We investigated these mechanisms and their specificity in distinct cell types by means of an interactome-based analysis of expression data.


Genes associated to the diseases were identified using data mining approaches, and their multimorbidity mechanisms in distinct cell types were characterized by means of an in silico analysis of the topology of the human interactome.


We characterized specific pathomechanisms for multimorbidities between asthma, dermatitis and rhinitis for distinct emergent non-eosinophilic cell types. We observed differential roles for cytokine signaling, TLR-mediated signaling and metabolic pathways for multimorbidities across distinct cell types. Furthermore, we also identified individual genes potentially associated to multimorbidity mechanisms.


Our results support the existence of differentiated multimorbidity mechanisms between asthma, dermatitis and rhinitis at cell type level, as well as mechanisms common to distinct cell types. These results will help understanding the biology underlying allergic multimorbidity, assisting in the design of new clinical studies.

Klíčová slova:

Blood – Immune receptor signaling – Interaction networks – Interleukins – Monocytes – Signal processing – T cells – Toll-like receptors


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