Unveiling chronic spontaneous urticaria pathophysiology through systems biology
Background: 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...
| Autores: | , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/69898 |
| Acceso en línea: | https://hdl.handle.net/10171/69898 |
| Access Level: | acceso abierto |
| Palabra clave: | Materias Investigacion::Ciencias de la Salud::Alergia Machine learning Artificial intelligence Chronic spontaneous urticaria Mast cells System biology |
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Unveiling chronic spontaneous urticaria pathophysiology through systems biologySegu-Verges, C. (Cristina)|||/items/ecd3db2a-b987-4b6f-9c99-a0756002a387Gómez. J. (Jessica)|||/items/3f8bf8c9-bdd6-46cb-b395-c37d4579b3e5Terradas-Montana, P. (Pau)|||/items/61cd14c0-848c-4fd2-b4d7-ee6dd14e36e4Artigas, L. (Laura)|||/items/5c6375e4-bfe1-4bdc-8502-1dd70e8b0437Smeets, S. (Serge)|||/items/de3d34f9-8322-492a-bc10-c5dae074e908Ferrer-Puga, M. (Marta)|||/items/ab9d3fc5-5095-4f28-8018-f157d8c9fce0Savic, S. (Sinisa)|||/items/f7a781c6-91fb-4282-9983-03fea73e7c46Materias Investigacion::Ciencias de la Salud::AlergiaMachine learningArtificial intelligenceChronic spontaneous urticariaMast cellsSystem biologyBackground: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.ElsevierDadun. Depósito Académico Digital Universidad de Navarra20242024-09-0920232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/69898reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/698982026-06-21T12:47:57Z |
| 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 Segu-Verges, C. (Cristina)|||/items/ecd3db2a-b987-4b6f-9c99-a0756002a387 Materias Investigacion::Ciencias de la Salud::Alergia Machine learning Artificial intelligence Chronic spontaneous urticaria Mast cells System biology |
| 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 |
Segu-Verges, C. (Cristina)|||/items/ecd3db2a-b987-4b6f-9c99-a0756002a387 Gómez. J. (Jessica)|||/items/3f8bf8c9-bdd6-46cb-b395-c37d4579b3e5 Terradas-Montana, P. (Pau)|||/items/61cd14c0-848c-4fd2-b4d7-ee6dd14e36e4 Artigas, L. (Laura)|||/items/5c6375e4-bfe1-4bdc-8502-1dd70e8b0437 Smeets, S. (Serge)|||/items/de3d34f9-8322-492a-bc10-c5dae074e908 Ferrer-Puga, M. (Marta)|||/items/ab9d3fc5-5095-4f28-8018-f157d8c9fce0 Savic, S. (Sinisa)|||/items/f7a781c6-91fb-4282-9983-03fea73e7c46 |
| author |
Segu-Verges, C. (Cristina)|||/items/ecd3db2a-b987-4b6f-9c99-a0756002a387 |
| author_facet |
Segu-Verges, C. (Cristina)|||/items/ecd3db2a-b987-4b6f-9c99-a0756002a387 Gómez. J. (Jessica)|||/items/3f8bf8c9-bdd6-46cb-b395-c37d4579b3e5 Terradas-Montana, P. (Pau)|||/items/61cd14c0-848c-4fd2-b4d7-ee6dd14e36e4 Artigas, L. (Laura)|||/items/5c6375e4-bfe1-4bdc-8502-1dd70e8b0437 Smeets, S. (Serge)|||/items/de3d34f9-8322-492a-bc10-c5dae074e908 Ferrer-Puga, M. (Marta)|||/items/ab9d3fc5-5095-4f28-8018-f157d8c9fce0 Savic, S. (Sinisa)|||/items/f7a781c6-91fb-4282-9983-03fea73e7c46 |
| author_role |
author |
| author2 |
Gómez. J. (Jessica)|||/items/3f8bf8c9-bdd6-46cb-b395-c37d4579b3e5 Terradas-Montana, P. (Pau)|||/items/61cd14c0-848c-4fd2-b4d7-ee6dd14e36e4 Artigas, L. (Laura)|||/items/5c6375e4-bfe1-4bdc-8502-1dd70e8b0437 Smeets, S. (Serge)|||/items/de3d34f9-8322-492a-bc10-c5dae074e908 Ferrer-Puga, M. (Marta)|||/items/ab9d3fc5-5095-4f28-8018-f157d8c9fce0 Savic, S. (Sinisa)|||/items/f7a781c6-91fb-4282-9983-03fea73e7c46 |
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author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Materias Investigacion::Ciencias de la Salud::Alergia Machine learning Artificial intelligence Chronic spontaneous urticaria Mast cells System biology |
| topic |
Materias Investigacion::Ciencias de la Salud::Alergia Machine learning Artificial intelligence Chronic spontaneous urticaria Mast cells System biology |
| description |
Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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 2023-01-01 2023 2023-01-01 2024 2024-09-09 |
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journal article http://purl.org/coar/resource_type/c_6501 |
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info:eu-repo/semantics/article |
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article |
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https://hdl.handle.net/10171/69898 |
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https://hdl.handle.net/10171/69898 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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