Transcriptomic profiling of chronic hand eczema skin reveals shared immune pathways and molecular drivers across subtypes.

Abstract

Chronic hand eczema (CHE) is a common skin disease with different subtypes, but knowledge of the molecular patterns associated with each subtype is limited. We sought to characterize the CHE transcriptome across subtypes. 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. We identified anatomic site-specific transcriptomic variations, showing unique characteristics in both healthy and CHE-affected palm skin. In CHE palms, we identified 2333 DEGs versus healthy palms. Upregulated genes predominantly involved keratinocyte host inflammation and immune signaling, while downregulated genes were linked to lipid metabolism and epidermal barrier function. IPA revealed numerous activated proinflammatory pathways, dominated by T_H1 and T_H2. 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. The lesional CHE transcriptome is primarily shared among subtypes and is characterized by activation of several immune pathways, dominated by T_H1 and T_H2. Key shared upstream regulators were identified, highlighting potential universal therapeutic targets.