Comprehensive proteome profiling of molecular endotypes in Japanese adults with moderate-to-severe atopic dermatitis
Frontiers in Medicine, 2025
Serelli-Lee V., Ozeki A., Preuss C., Benschop R., Torisu-Itakura H., Matsuo T., Sims J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Dermatological Diseases | Pathophysiology Patient Stratification | Serum |  Olink Explore 3072/384 |
Abstract
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 analysis 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 were 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.