{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:28:59Z","timestamp":1786573739509,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1AI151958"],"award-info":[{"award-number":["UM1AI151958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201000017C"],"award-info":[{"award-number":["HHSN272201000017C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI117673"],"award-info":[{"award-number":["U19AI117673"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Atopic Dermatitis (AD) is a chronic inflammatory skin disease characterized by complex pathogenesis, variable clinical phenotypes, and broad severity spectrum. We utilized a serum\u2010proteomic approach integrated with machine learning (ML) to identify novel biomarkers that distinguish mild from severe AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum from sixty\u2010seven AD adults, stratified by Eczema Area and Severity Index\/EASI and Rajka\u2010Langeland\/RJL into mild (\u2264\u20097 and \u2264\u20094, respectively;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200933) or severe (\u2265\u200920 and \u2265\u20098, respectively;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934), was analyzed with Olink Explore 3072. Differentially expressed proteins (DEPs) were identified using t\u2010tests and False Discovery Rate correction (FDR \u2264\u20090.05). Tissue enrichment analysis was conducted using HPAStainR. Pearson correlations were performed between DEPs and clinical variables, serum lactate dehydrogenase\/LDH and biomarkers for Th\u2010pathways. ML (TMLE\/SuperLearner, Boruta, MUVR) was used to identify top severity biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      469 DEPs distinguished severe vs. mild AD. DEPs were significantly enriched for epithelial proteins (e.g., skin, tonsil, and esophagus epithelium). Subsets correlated strongly with LDH (68 DEPs) and\/or Th2\/Th22 markers (90 DEPs;\n                      <jats:italic>r<\/jats:italic>\n                      \u2009\u2265\u20090.6, FDR \u2264\u20090.05). Nine serum proteins (CCL17, CCL22, DEFB4A\/B, EZR, GPR15L, IL22, PRSS53, SERPINB8, SETMAR) overlapped across three ML analyses as severity discriminating biomarkers (cross\u2010validated AUC\u2009=\u20090.989; 95% CI: 0.974\u20131.00).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Severe AD exhibits a proteomic footprint enriched in epithelial\u2010associated proteins that correlate with LDH\u2010associated tissue injury and\/or Th2\/Th22 pathways. In this cross\u2010sectional cohort, ML identified biomarkers that discriminated mild\/severe AD groups with high cross\u2010validated accuracy. Longitudinal and external validation studies, including healthy controls, are needed to determine specificity, generalizability, and prognostic utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70464","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:59:48Z","timestamp":1785491988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum\u2010Proteomic Profiling Reveals Distinct Atopic Dermatitis Severity\u2010Linked Signatures"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8096-4084","authenticated-orcid":false,"given":"Jag S.","family":"Lally","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0133-5067","authenticated-orcid":false,"given":"Takeshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2939-5080","authenticated-orcid":false,"given":"Shan","family":"Gao","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7922-2703","authenticated-orcid":false,"given":"Xueya","family":"Cai","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-3844","authenticated-orcid":false,"given":"Donald Y. M.","family":"Leung","sequence":"additional","affiliation":[{"name":"National Jewish Health  Denver Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-667X","authenticated-orcid":false,"given":"Lisa A.","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-435X","authenticated-orcid":false,"given":"Anna","family":"De Benedetto","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York 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