Skin tape sampling technique identifies proinflammatory cytokines in atopic dermatitis skin

Abstract

Background: Monitoring the effects of biologic therapies in skin diseases will benefit from alternative noninvasive skin sampling techniques to evaluate immune pathways in diseased tissue early and longitudinally.

Objective: To establish a minimally invasive profiling of skin cytokines for diagnosis, therapeutic response monitoring, and clinical research in atopic dermatitis (AD) and other skin diseases, particularly in pediatric cohorts.

Methods: We developed a novel method for cytokine profiling in the epidermis using skin tape strips (STSs) in a setting designed to maximize the efficiency of protein extraction from STSs. This method was applied to analyze STS protein extracts from the lesional skin of children having AD (n = 41) and normal, healthy controls (n = 22). A total of 20 cytokines were probed with the ultrasensitive Mesoscale multiplex cytokine assay.

Results: A significant increase in interleukin (IL)-1b (P < .01), IL-18 (P < .001), and IL-8 (P < .001) with a decrease in IL-1a (P < .001) in the stratum corneum of AD lesional skin was found. Concurrently, an increase in markers associated with type 2 inflammatory response was readily detectable in AD lesional skin, including C-C motif chemokine ligand (CCL) 22, CCL 17, and thymic stromal lymphopoietin (TSLP). The levels of IL-1b, IL-18, and TSLP exhibited positive correlations with the AD severity index (Scoring AD index) and skin transepidermal water loss (TEWL), whereas an inverse correlation between IL-1a and Scoring AD index and IL-1a and TEWL was found. The levels of CCL17, CCL22, TSLP, IL-22, and IL-17a correlated with skin TEWL measurements.

Conclusion: Using minimally invasive STS analysis, we identified cytokine profiles easily sampled in AD lesional skin. The expression of these markers correlated with disease severity and reflected changes in TEWL in lesional skin. These markers suggest new response assessment targets for AD skin.

Trial registration: ClinicalTrials.gov Identifier: NCT03168113.

Conflict of interest statement

Conflict of Interest: None

Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

eFigure 1.

Concentrations of protein extracts prepared from skin tape strip samples from lesional skin of ADFA+, AD FA- patients and NA controls. *p

eFigure 2.

Cytokine profiles of lesional skin of AD FA+ and AD FA- subjects as compared to NA controls. *p

Figure 1.

Skin tape strip (STS) sample collection. Adhesive STS (CuDerm; Ø22mm) are applied to the skin area of interest (A) with the standardized pressure device (D-Squame D500; 225 g/cm2) (B). Collected STS are adhered to glossy storage cards (CuDerm) (C, D) to minimize the air exposure of the collected biomaterial and cryopreserved at −80°C.

Figure 2.

Concentrations of protein extracts prepared from skin tape strip samples from lesional skin of AD patients and NA controls. ***p

Figure 3.

Cytokine profiles of AD lesional skin determines the changes in the proinflammatory and type 2 cytokine production in these skin samples as compared to skin samples from NA controls, with no significant effect on type 1/type 17 inflammatory pathway. *p

Figure 4.

A relationship between inflammatory mediators detected in AD lesional skin and AD disease severity index SCORAD.

Figure 5.

A correlation analysis reveals a relationship between inflammatory mediators detected in AD lesional skin and TEWL measurements from the sampled skin area.