{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:34:28Z","timestamp":1791588868809,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016492","name":"Kiniksa Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Prurigo nodularis (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>) is a severe, intensely pruritic subtype of chronic prurigo for which the molecular basis and interplay between pathophysiologic mechanisms and clinical manifestations are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LOTUS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content> was a longitudinal observational study that included 54 participants from 11 centers and was designed to improve disease understanding. Protein expression, histology and <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Histologically, all patients had typical <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content> characteristics. Immunohistochemically, and on the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level, expression in lesional versus non\u2010lesional samples for <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201031 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) was significantly higher. In addition, immunohistochemistry showed higher expression of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">31RA<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), <jats:styled-content style=\"fixed-case\">OSM<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and <jats:styled-content style=\"fixed-case\">OSMR\u00df<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content> lesional skin showed higher expression of Th2 and Th17\/Th22 pathway markers. A correlation analysis of gene expression highlighted two groups of intra\u2010marker correlations dividing the Th2 markers, the first containing barrier and regulatory genes and the other containing markers of general inflammation that correlated negatively and positively with Th17\/Th22 genes, respectively. Correlations between gene expression and <jats:styled-content style=\"fixed-case\">NRS<\/jats:styled-content> scores were weak and involved genes associated with general inflammation (<jats:styled-content style=\"fixed-case\"><jats:italic>MMP12<\/jats:italic><\/jats:styled-content>) and Th2 (<jats:styled-content style=\"fixed-case\"><jats:italic>IL10<\/jats:italic><\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>CCL18<\/jats:italic><\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>IL4R<\/jats:italic><\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study confirms the role of Th2 signature in PN and the dominant role of IL31. Correlation analysis of gene expression showed differing relationships between subsets of the Th2 axis with Th1 and Th17\/Th22 markers, highlighting the potential of different components of the Th2 pathway to interact with and modulate other immune axes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.20812","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T09:56:32Z","timestamp":1751450192000},"page":"1750-1759","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Th2 <scp>mRNA<\/scp> gene expression analysis separates Prurigo nodularis into two immune signature groups"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-7786","authenticated-orcid":false,"given":"Sonja","family":"St\u00e4nder","sequence":"first","affiliation":[{"name":"Pruritus Medicine Section, Department of Dermatology, and Center for Chronic Pruritus (KCP) University Hospital of 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for Chronic Pruritus (KCP) University Hospital of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-6683","authenticated-orcid":false,"given":"Dieter","family":"Metze","sequence":"additional","affiliation":[{"name":"Pruritus Medicine Section, Department of Dermatology, and Center for Chronic Pruritus (KCP) University Hospital of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-3631","authenticated-orcid":false,"given":"Madeline","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology Icahn School of Medicine at Mount Sinai  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-8536","authenticated-orcid":false,"given":"Ester","family":"Del Duca","sequence":"additional","affiliation":[{"name":"Department of 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