Endotype classification of atopic dermatitis patients using immunohistochemistry and scRNA-seq for pSTAT6 targeting immunotherapy 4730

Abstract Description Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disorder with the most effective treatment achieving efficacy rates of 60-70%. This highlights a pressing need for new therapeutics with higher efficacy, particularly in non-responders. However, there is no established strategy for endotype classification to guide the development of clinical trials for future treatments. Thus, we aim to construct a predictive system comprising various biomarkers that could stratify patients for existing and newly developed drugs. In this study, we first focused on phosphorylated-signal transducer and activator of transcription-6 (pSTAT6), a key regulator of Th2 cell polarization and AD, and addressed pSTAT6 as a potential target. We quantified pSTAT6 expression in skin biopsies of 32 AD patients using immunohistochemistry (IHC) and stratified them into pSTAT6-high and pSTAT6-low groups. We also performed single-cell RNA sequencing (scRNA-seq) on skin biopsies among 13 patients to unbiasedly profile gene expression patterns across cell types. Furthermore, we investigated a correlation of selected gene sets including IL-18 with pSTAT6 expression levels quantified by IHC. These findings suggest that stratifying patients based on gene sets identified in this study could significantly aid the design of clinical trials for potential treatment options targeting pSTAT6. Topic Categories Immune Mechanisms of Human Disease (HUM)