{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:57:07Z","timestamp":1787727427985,"version":"build-2784847793"},"reference-count":28,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["GSE148346"],"award-info":[{"award-number":["GSE148346"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Alopecia areata (AA) is a chronic autoimmune disorder characterized by non-scarring hair loss, with subtypes ranging from patchy alopecia (AAP) to alopecia totalis and universalis (AT\/AU). The aim of this research is to investigate molecular features across AA severity by performing an integrated analysis of scalp transcriptomic datasets (GSE148346, GSE68801, GSE45512, GSE111061) and matched serum proteomic data from GSE148346. Differential expression analysis indicated that, relative to normal scalp, non-lesional AA tissue shows early immune activation\u2014including Type 1 (C-X-C motif chemokine ligand 9 (CXCL9), CXCL10, CD8a molecule (CD8A), C-C motif chemokine ligand 5 (CCL5)) and Type 2 (CCL13, CCL18) signatures\u2014together with reduced expression of hair-follicle structural genes (keratin 32(KRT32)\u201335, homeobox C13 (HOXC13)) (FDR &lt; 0.05, |fold change| &gt; 1.5). Lesional AAP and AT\/AU scalp showed stronger pro-inflammatory upregulation and greater loss of keratins and keratin-associated proteins (KRT81, KRT83, desmoglein 4 (DSG4), KRTAP12\/15) compared with non-lesional scalp (FDR &lt; 0.05, |fold change| &gt; 1.5). Ferroptosis-associated genes (cAMP responsive element binding protein 5 (CREB5), solute carrier family 40 member 1 (SLC40A1), (lipocalin 2) LCN2, SLC7A11) and IRS (inner root sheath) differentiation genes (KRT25, KRT27, KRT28, KRT71\u2013KRT75, KRT81, KRT83, KRT85\u201386, trichohyalin (TCHH)) were consistently repressed across subtypes, with the strongest reductions in AT\/AU lesions versus AAP lesions, suggesting that oxidative-stress pathways and follicular structural integrity may contribute to subtype-specific pathology. Pathway analysis of lesional versus non-lesional scalp highlighted enrichment of IFN-\u03b1\/\u03b3, cytotoxic, and IL-15 signaling. Serum proteomic profiling, contrasting AA vs. healthy controls, corroborated scalp findings, revealing parallel alterations in immune-related proteins (CXCL9\u2013CXCL10, CD163, interleukin-16 (IL16)) and structural markers (angiopoietin 1 (ANGPT1), decorin (DCN), chitinase-3-like protein 1 (CHI3L1)) across AA subtypes. Together, these data offer an integrated view of immune, oxidative, and structural changes in AA and found ferroptosis-related and IRS genes, along with immune signatures, as potential molecular indicators to support future studies on disease subtypes and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26199662","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:22:47Z","timestamp":1759483367000},"page":"9662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated Meta-Analysis of Scalp Transcriptomics and Serum Proteomics Defines Alopecia Areata Subtypes and Core Disease Pathways"],"prefix":"10.3390","volume":"26","author":[{"given":"Li","family":"Xi","sequence":"first","affiliation":[{"name":"Pfizer Inc., Portland St., Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Peeva","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Portland St., Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-2662","authenticated-orcid":false,"given":"Yuji","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Collegeville, PA 19426, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-0382","authenticated-orcid":false,"given":"Zhan","family":"Ye","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Portland St., Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Hyde","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Portland St., Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Guttman-Yassky","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2017.04.1141","article-title":"Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis","volume":"78","author":"Strazzulla","year":"2018","journal-title":"J. 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