ORIGINAL RESEARCH article
Front. Med.
Sec. Dermatology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1649918
This article is part of the Research TopicAdvancing the Understanding and Management of Immune Skin Conditions Through Multiomic ApproachesView all 5 articles
Comprehensive Proteome Profiling of Molecular Endotypes in Japanese Adults with Moderate-to-Severe Atopic Dermatitis
Provisionally accepted
Victoria Serelli-Lee1*
Akichika Ozeki1Christoph Preuss2Robert J Benschop2Hitoe Torisu- Itakura1Takashi Matsuo1
Jonathan Sims2- 1Eli Lilly Japan K.K, Kobe, Japan
- 2Eli Lilly and Company, Indianapolis, United States
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Introduction: 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. Methods: Serum samples from Japanese patients with moderate-to-severe AD (n=73) enrolled in a phase 3 study of baricitinib (BREEZE-AD2; NCT03334422) and samples from healthy controls (n=15) were analyzed using the Olink Explore 1536 assay. Patient clusters were identified through k-means clustering. Differential expression and weighted gene co-expression network analysis were performed for in-depth examination of proteomic profiles. Results: 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—including 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—were 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 also correlated with skin-based disease severity scores. Conclusion: 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.
Keywords: atopic dermatitis, biomarkers, Endotype, Inflammation, Proteomics, computational
Received: 19 Jun 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Serelli-Lee, Ozeki, Preuss, Benschop, Torisu- Itakura, Matsuo and Sims. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Victoria Serelli-Lee, lee_victoria@lilly.com
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