In silico Identification of immune cell-types and pathways involved in chronic spontaneous urticaria

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• dc.contributor.author Prosty, Connor
• dc.contributor.author Gabrielli, Sofianne
• dc.contributor.author Ben-Shoshan, Moshe
• dc.contributor.author Le, Michelle
• dc.contributor.author Giménez Arnau, Anna Maria
• dc.contributor.author Litvinov, Ivan V.
• dc.contributor.author Lefrançois, Philippe
• dc.contributor.author Netchiporouk, Elena
• dc.date.accessioned 2023-02-10T07:27:56Z
• dc.date.available 2023-02-10T07:27:56Z
• dc.date.issued 2022
• dc.description.abstract Background: the immunopathogenesis of chronic spontaneous urticaria (CSU) is poorly understood, but recent research suggests that patients can be divided into autoallergic and autoimmune subtypes. Given that not all patients can be controlled with current treatment regimens, including anti-IgE monoclonal antibodies, a better understanding of the immune pathways involved in CSU may enable the repurposing of monoclonal antibodies used for other dermatologic diseases (e.g., Th2 and Th17 inhibitors). Therefore, we investigated the implicated immune cells and pathways by reanalyzing publicly available transcriptomic data. Methods: Microarray data of CSU and healthy control (HC) skin and blood were obtained from the Gene Expression Omnibus (GSE72542, GSE57178). Differentially expressed genes were defined as a false discovery rate <0.05 and a |log2 fold change| ≥1. Pathway analyses were conducted using ToppGene and KEGG. Cell-type enrichment was determined by CIBERSORT and xCell and was correlated with clinical characteristics. Results: Th2 (IL-4/13 signaling) and Th17-related (IL-17/23 signaling) pathways were upregulated in lesional compared to non-lesional and HC samples. In non-lesional versus lesional samples, CIBERSORT analysis revealed increased regulatory T-cells (Treg) and resting mast cells. xCell analysis established that Th1 and Th2 scores were not significantly different between lesional and HC samples. However, Th2 scores in both lesional and non-lesional samples correlated positively with disease severity. Few differentially expressed genes and pathways were identified between CSU and HC blood samples. Conclusion: our results support the involvement of Th2 and Th17-related genes and pathways in CSU. Th2 scores associate with disease severity, which indicates the clinical relevance of these findings. Increased resting mast cell and Treg scores in non-lesional samples may suggest local suppression of wheal formation. Moreover, disease activity seemed to be restricted to the skin as there were limited findings from blood. Larger studies using next-generation sequencing will be helpful to confirm these results.
• dc.format.mimetype application/pdf
• dc.identifier.citation Prosty C, Gabrielli S, Ben-Shoshan M, Le M, Giménez-Arnau AM, Litvinov IV, et al. In silico Identification of immune cell-types and pathways involved in chronic spontaneous urticaria. Front Med (Lausanne). 2022 Jul 7; 9: 926753. DOI: 10.3389/fmed.2022.926753
• dc.identifier.doi http://dx.doi.org/10.3389/fmed.2022.926753
• dc.identifier.issn 2296-858X
• dc.identifier.uri http://hdl.handle.net/10230/55707
• dc.language.iso eng
• dc.publisher Frontiers
• dc.rights Copyright © 2022 Prosty, Gabrielli, Ben-Shoshan, Le, Giménez-Arnau, Litvinov, Lefrançois and Netchiporouk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Th17
• dc.subject.keyword Th2
• dc.subject.keyword Autoallergy
• dc.subject.keyword Autoimmunity
• dc.subject.keyword Chronic idiopathic urticaria
• dc.subject.keyword Chronic spontaneous urticaria
• dc.subject.keyword Chronic urticaria
• dc.subject.keyword Pathogenesis
• dc.title In silico Identification of immune cell-types and pathways involved in chronic spontaneous urticaria
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion