Vesicular hand eczema transcriptome analysis provides insights into its pathophysiology

Abstract

Hand eczema is a common inflammatory skin condition of the hands whose pathogenesis is largely unknown. More insight and knowledge of the disease on a more fundamental level might lead to a better understanding of the biological processes involved, which could provide possible new treatment strategies. We aimed to profile the transcriptome of lesional palmar epidermal skin of patients suffering from vesicular hand eczema using RNA-sequencing. RNA-sequencing was performed to identify differentially expressed genes in lesional vs. non-lesional palmar epidermal skin from a group of patients with vesicular hand eczema compared to healthy controls.Comprehensive real-time quantitative PCR analyses and immunohistochemistry were used for validation of candidate genes and protein profiles for vesicular hand eczema.Overall, a significant and high expression of genes/proteins involved in keratinocyte host defense and inflammation was found in lesional skin. Furthermore, we detected several molecules, both up or downregulated in lesional skin, which are involved in epidermal differentiation. Immune signalling genes were found to be upregulated in lesional skin, albeit with relatively low expression levels. Non-lesional patient skin showed no significant differences compared to healthy control skin. Lesional vesicular hand eczema skin shows a distinct expression profile compared to non-lesional skin and healthy control skin. Notably, the overall results indicate a large overlap between vesicular hand eczema and earlier reported atopic dermatitis lesional transcriptome profiles, which suggests that treatments for atopic dermatitis could also be effective in (vesicular) hand eczema.

The long‐term effect of dupilumab on chronic hand eczema in patients with moderate to severe atopic dermatitis—52 week results from the Dutch BioDay Registry

“…This positive effect on HE has also been shown in several case reports in isolated, nonatopic HE, including vesicular HE, hyperkeratotic HE, allergic contact dermatitis, and ICD 7,18 . Furthermore, in a recently published study, in which we analysed the transcriptome of vesicular HE through RNA‐sequencing, it was found that IL4R was also highly upregulated in lesional HE skin compared with healthy control skin 19 . This suggests that the IL‐4/IL‐13 pathway might also be involved in isolated HE.…”

“…7,18 Furthermore, in a recently published study, in which we analysed the transcriptome of vesicular HE through RNA-sequencing, it was found that IL4R was also highly upregulated in lesional HE skin compared with healthy control skin. 19 This suggests that the IL-4/IL-13 pathway might also be involved in isolated HE. These overlaps in pathways between the AD transcriptome and HE transcriptome, and results from previously published case reports and case series in isolated HE, hold promise for dupilumab to be a suitable treatment for moderate to severe CHE in the future.…”

Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice

“…However, transcriptomic profiles of human skin diseases used for comparison are mostly derived from human hairy skin – a difference that needs to be taken into account when interpreting the presented comparisons between mouse and human skin. This is why we additionally selected transcriptomic studies on skin diseases affecting human glabrous skin, that is, palms and soles, such as handfoot psoriasis ( Ahn et al, 2018 ), palmoplantar pustulosis ( McCluskey et al, 2022 ), and vesicular hand eczema ( Voorberg et al, 2021 ). Among top gene signatures presented in glabrous skin datasets (2498 DEGs), 928 proteins were quantified in our paw skin datasets and 96 of them showed age and/or sex dependency including several collagens ( Figure 6—source data 3 ; examples are marked with ‘#’ in Figure 6C ).…”

Transcriptional differences between vesicular hand eczema and atopic dermatitis

“…Read sequences were already trimmed before by BaseClear B.V. (Leiden, The Netherlands) as previously described. 5 The trimmed read sequences were subsequently aligned to the human reference genome sequence (GRCh38; Ensembl release 103) using STAR (version 2.7.8a). 7 For more details on the settings used in this study, see Supporting information.…”

“…5 Both diseases exhibit an upregulation of genes involved in keratinocyte host defence, inflammation, and immune signalling, while simultaneously downregulated genes are involved in skin barrier function. 5 However, the DEGs that differentiate VHE from AD are unknown. Characterization of these DEGs would provide more insight into the pathogenesis of HE.…”