Transcriptomic profiling of chronic hand eczema skin reveals shared immune pathways and molecular drivers across subtypes
Anna Sophie Quaade, Thomas Litman, Xing Wang, Christine Becker, B.D. McCauley, Julie Sølberg, Jacob P. Thyssen, Jeanne Duus Johansen
Abstract
BACKGROUND: Chronic hand eczema (CHE) is a common skin disease with different subtypes, but knowledge of the molecular patterns associated with each subtype is limited. OBJECTIVE: We sought to characterize the CHE transcriptome across subtypes. METHODS: Using RNA sequencing, we studied the transcriptome of 220 full-thickness skin biopsy samples collected from palms, dorsa, and arms from 96 patients with CHE and/or atopic dermatitis (AD) and 32 healthy controls. The primary analysis focused on 16 healthy and 54 lesional CHE palm samples that were further stratified by AD status and unique etiology. Differentially expressed genes (DEGs) were identified across the cohort, and Ingenuity Pathway Analysis (IPA) was used for pathway analysis and upstream regulator prediction. RESULTS: 2. Key upstream regulators included type 1 (IFN-γ, TNF, STAT1, IL-2) and type 2 (IL-4) associated molecules, and IL-1β. Lesional palm signatures were broadly shared across CHE subtypes. No DEGs were found between allergic and irritant contact dermatitis CHE. Subtype-specific pathway and upstream regulator activity variations were noted. CONCLUSION: 2. Key shared upstream regulators were identified, highlighting potential universal therapeutic targets.