{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:47:05Z","timestamp":1763653625041,"version":"3.45.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Atopic dermatitis (AD) is an inflammatory skin disease that is heterogeneous in clinical presentation and biological mechanisms. Several studies have suggested biomarker-defined molecular endotypes in AD. This study aimed to characterize potential endotypes in Japanese patients with moderate-to-severe AD and comprehensively evaluate their circulating protein profiles to better understand disease etiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum samples from Japanese patients with moderate-to-severe AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f73) enrolled in a phase 3 study of baricitinib (BREEZE-AD2; NCT03334422) and samples from healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f15) were analyzed using the Olink Explore 1536 assay. Patient clusters were identified through\n                      <jats:italic>k<\/jats:italic>\n                      -means clustering. Differential expression analysis and weighted gene co-expression network analysis were performed for in-depth examination of proteomic profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two patient clusters, characterized by high (AD_HI) and low (AD_LO) inflammatory profiles, were found to be stable and reproducible. Canonical AD inflammatory mediators\u2014including interleukin (IL)-13, IL-19, pulmonary and activation-regulated chemokine (PARC), thymus and activation-regulated chemokine (TARC), chemokine (C-C motif) ligand (CCL)22, CCL26, and CCL27\u2014were upregulated in both clusters, with greater upregulation in the AD_HI cluster. Additionally, proteins not typically associated with AD-related inflammation were upregulated in AD_HI patients. The AD_HI cluster was associated with protein networks representing a range of immune and non-immune pathways. Dysregulated protein signatures associated with the AD_HI cluster were also correlated with skin-based disease severity scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study characterizes the circulating proteome and clinical characteristics across putative molecular endotypes in AD. The findings corroborate current knowledge on AD pathophysiology and suggest other axes of dysregulation in a subset of patients with AD. These results may support the development of personalized therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1649918","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T15:44:00Z","timestamp":1763653440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive proteome profiling of molecular endotypes in Japanese adults with moderate-to-severe atopic dermatitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Victoria","family":"Serelli-Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akichika","family":"Ozeki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Preuss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Benschop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoe","family":"Torisu-Itakura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan T.","family":"Sims","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.jaci.2020.04.062","article-title":"Confirmation of multiple endotypes in atopic dermatitis based on serum biomarkers","volume":"147","author":"Bakker","year":"2021","journal-title":"J Allergy Clin 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