{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:22:27Z","timestamp":1790706147375,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007475","name":"Canadian Dermatology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007475","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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 &amp;lt;0.05 and a |log\n                      <jats:sub>2<\/jats:sub>\n                      fold change| \u22651. Pathway analyses were conducted using ToppGene and KEGG. Cell-type enrichment was determined by CIBERSORT and xCell and was correlated with clinical characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2022.926753","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T12:14:49Z","timestamp":1657196089000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["In silico Identification of Immune Cell-Types and Pathways Involved in Chronic Spontaneous Urticaria"],"prefix":"10.3389","volume":"9","author":[{"given":"Connor","family":"Prosty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofianne","family":"Gabrielli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Ben-Shoshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Gim\u00e9nez-Arnau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan V.","family":"Litvinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lefran\u00e7ois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Netchiporouk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1111\/all.13397","article-title":"The EAACI\/GA2LEN\/EDF\/WAO guideline for the definition, classification, diagnosis and management of urticaria.","volume":"73","author":"Zuberbier","year":"2018","journal-title":"Allergy."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1111\/all.13209","article-title":"The burden of chronic spontaneous urticaria is substantial: real-world evidence from ASSURE-CSU.","volume":"72","author":"Maurer","year":"2017","journal-title":"Allergy."},{"key":"B3","doi-asserted-by":"publisher","first-page":"187","DOI":"10.2147\/JAA.S249765","article-title":"Management of pediatric chronic spontaneous urticaria: a review of current evidence and guidelines.","volume":"14","author":"Chang","year":"2021","journal-title":"J Asthma Allergy."},{"key":"B4","doi-asserted-by":"publisher","first-page":"326","DOI":"10.4168\/aair.2012.4.6.326","article-title":"Treatment of chronic spontaneous urticaria.","volume":"4","author":"Kaplan","year":"2012","journal-title":"Allergy Asthma Immunol Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1001\/jamadermatol.2018.3447","article-title":"Benefits and harms of omalizumab treatment in adolescent and adult patients with chronic idiopathic (spontaneous) urticaria: a meta-analysis of \u201creal-world\u201d evidence.","volume":"155","author":"Tharp","year":"2019","journal-title":"JAMA Dermatol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00627","article-title":"Autoimmune theories of chronic spontaneous urticaria.","volume":"10","author":"Bracken","year":"2019","journal-title":"Front Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.jaci.2016.08.050","article-title":"Autoimmune chronic spontaneous urticaria: what we know and what we do not know.","volume":"139","author":"Kolkhir","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1172\/JCI511","article-title":"Anti-fcepsilonrialpha autoantibodies in autoimmune-mediated disorders. 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