Non-invasive epidermal proteome assessment-based diagnosis and molecular subclassification of psoriasis and eczematous dermatitis

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Abstract

Background

Immunologic heterogeneity is known to exist within both eczematous dermatitis and psoriasis; however, selection of molecularly targeted therapies for individual patients generally does assess for or incorporate such information about patient-specific immune changes.

Objective

We sought to develop a rapid, non-invasive method for obtaining and analyzing epidermal protein biomarkers from skin and utilize this methodology to dissect immunologic heterogeneity in both psoriasis and eczematous dermatitis.

Methods

We optimize and evaluate detergent-based immune profiling system (DIPS) which utilizes a combination of two detergents to solubilize full-thickness epidermis when applied to the skin with an applicator. Downstream proteomic profiling of this material allows high-throughput immunologic characterization of immune biomarkers.

Results

DIPS was performed on 43 patients with psoriasis and 27 patients with eczematous dermatitis. This approach was found to be painless, nonscarring, and enabled rapid turnaround from sample collection to data output. We used this approach to accurately differentiate psoriasis and eczema using a limited set of proteins and to identify cases of eczema/psoriasis overlap with non-canonical molecular profiles. Additionally, we measured patient-specific cytokine profiles in eczema that correlated with response to IL-4Rα blockade.

Conclusion

DIPS is a promising new non-invasive cutaneous immune profiling approach that can deconvolute immune heterogeneity amongst patients with both psoriasis and eczematous dermatitis.

Clinical Implication

DIPS has potential applications in both research and day-to-day dermatologic practice and may help personalize diagnosis and medication selection in patients with inflammatory skin diseases.

Capsule summary

Detergent-based immune profiling system (DIPS), a novel non-invasive approach for molecular evaluation of skin disease, is described and evaluated in psoriasis and eczematous dermatitis

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  1. Skin was swabbed using a microfiber cosmetic applicator and approximately 40µL of surfactant. Swabbing was performed by rubbing the surfactant-coated applicator tip in a back-and-forth motion for 45 seconds, applying light pressure, over a 2mm-by-1mm rectangular area on lesional psoriasis or eczema skin.

    What an interesting study, especially the findings relating to patient biomarkers and predicted therapeutic responsiveness.

    A few questions arose for me: 1) for the swabbing procedure, how were the affected areas chosen? Were they on similar body parts/skin types? Did this differ for psoriatic or eczematic skin? This information in the Methods section could be informative for readers. 2) Did you test for intra-patient proteomic consistency by sampling more than once per patient? I'm interested in how intra- and inter-patient heterogeneity might differ from each other, affect clustering, or inform overall conclusions. 3) Similarly, could you compare to swabs/proteomics from non-affected skin areas from the same patients? 4) How do you think disease progression dynamics might also introduce noise in proteomics, i.e. could some of the differences in results be explained by sampling from different timepoints?