Unveiling chronic spontaneous urticaria pathophysiology through systems biology

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• dc.contributor.author Segú-Vergés, Cristina
• dc.contributor.author Gómez, Jessica
• dc.contributor.author Terradas-Montana, Pau
• dc.contributor.author Artigas, Laura
• dc.contributor.author Smeets, Serge
• dc.contributor.author Ferrer, Marta
• dc.contributor.author Savic, Sinisa
• dc.date.accessioned 2023-06-06T06:02:52Z
• dc.date.available 2023-06-06T06:02:52Z
• dc.date.issued 2023
• dc.description.abstract Chronic spontaneous urticaria (CSU) is a rare, heterogeneous, severely debilitating, and often poorly controlled skin disease resulting in an itchy eruption that can be persistent. Antihistamines and omalizumab, an anti-IgE mAb, are the only licensed therapies. Although CSU pathogenesis is not yet fully understood, mast cell activation through the IgE:high-affinity IgE receptor (FcεRI) axis appears central to the disease process. We sought to model CSU pathophysiology and identify in silico the mechanism of action of different CSU therapeutic strategies currently in use or under development. Therapeutic performance mapping system technology, based on systems biology and machine learning, was used to create a CSU interactome validated with gene expression data from patients with CSU and a CSU model that was used to evaluate CSU pathophysiology and the mechanism of action of different therapeutic strategies. Our models reflect the known role of mast cell activation as a central process of CSU pathophysiology, as well as recognized roles for different therapeutic strategies in this and other innate and adaptive immune processes. They also allow determining similarities and differences between them; anti-IgE and Bruton tyrosine kinase inhibitors play a more direct role in mast cell biology through abrogation of FcεRI signaling activity, whereas anti-interleukins and anti–Siglec-8 have a role in adaptive immunity modulation. In silico CSU models reproduced known CSU and therapeutic strategies features. Our results could help advance understanding of therapeutic mechanisms of action and further advance treatment research by patient profile.
• dc.format.mimetype application/pdf
• dc.identifier.citation Segú-Vergés C, Gómez J, Terradas-Montana P, Artigas L, Smeets S, Ferrer M, et al. Unveiling chronic spontaneous urticaria pathophysiology through systems biology. Journal of Allergy and Clinical Immunology. 2023 Apr;151(4):1005-14. DOI: 10.1016/j.jaci.2022.12.809
• dc.identifier.doi http://dx.doi.org/10.1016/j.jaci.2022.12.809
• dc.identifier.issn 0091-6749
• dc.identifier.uri http://hdl.handle.net/10230/57038
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Journal of Allergy and Clinical Immunology. 2023 Apr;151(4):1005-14
• dc.rights © 2023 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Machine learning
• dc.subject.keyword Chronic spontaneous urticaria
• dc.subject.keyword System biology
• dc.subject.keyword Artificial intelligence
• dc.subject.keyword Mast cells
• dc.title Unveiling chronic spontaneous urticaria pathophysiology through systems biology
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion