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RNA-Seq in peripheral blood samples of atopic dermatitis patients of the TREATgermany registry before and after initiation of systemic therapy with Dupilumab

ABSTRACT: Background: Few studies have analyzed the blood transcriptome in atopic dermatitis (AD). Objective: We explored blood transcriptomic features of moderate to severe AD. Results: AD patients showed pronounced inflammatory expression signatures with increased myeloid and IL-5-related patterns, and clearly segregated into 2 distinct clusters, with striking differences in particular for transcripts involved in eosinophil signaling. The eosinophil-high endotype showed a more pronounced global dysregulation, a positive correlation between disease activity and signatures related to IL-5 signaling, and strong correlations with several target proteins of antibodies or small molecules under development for AD. In contrast, the eosinophil-low endotype showed little transcriptomic dysregulation and no association between disease activity and gene expression. Clinical improvement with receipt of dupilumab was accompanied by a decrease of innate immune responses and an increase of lymphocyte signatures including B-cell activation and natural killer cell composition and/or function. The proportion of super responders was higher in the eosinophil-low endotype (32% vs 11%). Continued downregulation of IL18RAP, IFNG, and granzyme A in the eosinophil-high endotype suggests a residual disturbance of natural killer cell function despite clinical improvement. Conclusion: AD can be stratified into eosinophilic and noneosinophilic endotypes; such stratification may be useful when assessing stratified trial designs and treatment strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208405 | GEO | 2022/07/21

REPOSITORIES: GEO

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