Unveiling chronic spontaneous urticaria pathophysiology through systems biology

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 f...

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Autores: Segú-Vergés, Cristina, Gómez, Jessica, Terradas-Montana, Pau, Artigas, Laura, Smeets, Serge, Ferrer, Marta, Savic, Sinisa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/57038
Acceso en línea:http://hdl.handle.net/10230/57038
http://dx.doi.org/10.1016/j.jaci.2022.12.809
Access Level:acceso abierto
Palabra clave:Machine learning
Chronic spontaneous urticaria
System biology
Artificial intelligence
Mast cells
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spelling Unveiling chronic spontaneous urticaria pathophysiology through systems biologySegú-Vergés, CristinaGómez, JessicaTerradas-Montana, PauArtigas, LauraSmeets, SergeFerrer, MartaSavic, SinisaMachine learningChronic spontaneous urticariaSystem biologyArtificial intelligenceMast cellsChronic 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.Elsevier202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/57038http://dx.doi.org/10.1016/j.jaci.2022.12.809reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJournal of Allergy and Clinical Immunology. 2023 Apr;151(4):1005-14© 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/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/570382026-05-29T05:05:01Z
dc.title.none.fl_str_mv Unveiling chronic spontaneous urticaria pathophysiology through systems biology
title Unveiling chronic spontaneous urticaria pathophysiology through systems biology
spellingShingle Unveiling chronic spontaneous urticaria pathophysiology through systems biology
Segú-Vergés, Cristina
Machine learning
Chronic spontaneous urticaria
System biology
Artificial intelligence
Mast cells
title_short Unveiling chronic spontaneous urticaria pathophysiology through systems biology
title_full Unveiling chronic spontaneous urticaria pathophysiology through systems biology
title_fullStr Unveiling chronic spontaneous urticaria pathophysiology through systems biology
title_full_unstemmed Unveiling chronic spontaneous urticaria pathophysiology through systems biology
title_sort Unveiling chronic spontaneous urticaria pathophysiology through systems biology
dc.creator.none.fl_str_mv Segú-Vergés, Cristina
Gómez, Jessica
Terradas-Montana, Pau
Artigas, Laura
Smeets, Serge
Ferrer, Marta
Savic, Sinisa
author Segú-Vergés, Cristina
author_facet Segú-Vergés, Cristina
Gómez, Jessica
Terradas-Montana, Pau
Artigas, Laura
Smeets, Serge
Ferrer, Marta
Savic, Sinisa
author_role author
author2 Gómez, Jessica
Terradas-Montana, Pau
Artigas, Laura
Smeets, Serge
Ferrer, Marta
Savic, Sinisa
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Machine learning
Chronic spontaneous urticaria
System biology
Artificial intelligence
Mast cells
topic Machine learning
Chronic spontaneous urticaria
System biology
Artificial intelligence
Mast cells
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/57038
http://dx.doi.org/10.1016/j.jaci.2022.12.809
url http://hdl.handle.net/10230/57038
http://dx.doi.org/10.1016/j.jaci.2022.12.809
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Allergy and Clinical Immunology. 2023 Apr;151(4):1005-14
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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