A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Hulshof, Lies; Hack, Dietrich; Hasnoe, Q.C.J.; Dontje, B.; Jakaša, Ivone; Riethmüller, Christoph; McLean, William; Aalderen, W. M. C. van; Land, Belinda van‘t; Kežić, Sanja; Sprikkelman, Alida; Middelkamp‐Hup, Maritza A.

doi:10.1111/bjd.16994

Br J Dermatol

2018

DOI: 10.1111/bjd.16994

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A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Lies Hulshof

Dietrich Hack

Q.C.J. Hasnoe

et al.

Abstract: Minimally invasive tape-stripping is suitable for the determination of many inflammatory mediators and skin barrier biomarkers in children with AD. This study shows differences between children with AD with skin type II and skin type VI in NMF levels, suggesting that some aspects of pathophysiological mechanisms may differ in AD children with light versus dark skin types.

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Cited by 59 publications

(102 citation statements)

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“…They reported that protein levels of interleukin (IL)‐1β, IL‐18, CXCL8, CCL2, CCL17 and CCL22 were significantly higher in the SC of lesional AD skin than in nonlesional AD and control healthy skin. Notably, the clinical severity of AD is associated with CXCL8, CCL2 and CCL17 levels in the SC . NMF levels in SC were comparable among healthy, nonlesional AD and lesional AD skin.…”

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confidence: 90%

“…NMF levels in SC were comparable among healthy, nonlesional AD and lesional AD skin. However, subgroup analysis revealed that patients with AD with skin type II exhibited reduced NMF levels compared with those with skin type IV in both nonlesional and lesional SC …”

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confidence: 92%

“…The principal source of NMF is filaggrin . Although NMF levels in the SC are not significantly decreased in patients with AD compared with healthy controls, patients with AD with light skin have lower levels of NMF than those with dark skin . A profiling study by Noda et al .…”

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confidence: 99%

“…In this issue of the BJD , Hulshof et al . report the assessment of protein levels of 28 cytochemokines and natural moisturizing factor (NMF) in tape‐stripped stratum corneum (SC) specimens of healthy individuals and patients with atopic dermatitis (AD) . They reported that protein levels of interleukin (IL)‐1β, IL‐18, CXCL8, CCL2, CCL17 and CCL22 were significantly higher in the SC of lesional AD skin than in nonlesional AD and control healthy skin.…”

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confidence: 99%

“…The SC plays a critical role in maintaining skin barrier function. Atopic inflammation preferentially driven by T‐helper type 2 cytokine IL‐4/IL‐13 deters the structural and molecular integrity of the SC including a downregulation of filaggrin . CCL17 and CCL22 are produced from keratinocytes and dendritic cells on stimulation with IL‐4/IL‐13 .…”

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confidence: 99%

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Useful components in the stratum corneum for assessment of atopic dermatitis

Furue

2019

Br J Dermatol

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confidence: 90%

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confidence: 92%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Useful components in the stratum corneum for assessment of atopic dermatitis

Furue

2019

Br J Dermatol

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Stripping Away Barriers to Find Relevant Skin Biomarkers for Pediatric Atopic Dermatitis

Castelo‐Soccio

2019

JAMA Dermatol

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Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis

et al. 2019

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IMPORTANCE Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. OBJECTIVE To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. MAIN OUTCOMES AND MEASURES Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (T H 2; IL-4, IL-13, and chemokines CCL17 and CCL26), and T H 17/T H 22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was −15.2 (0.91) and normal was −19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) −2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and T H 2 (IL-33 and IL-4R) and T H 17/T H 22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). CONCLUSIONS AND RELEVANCE In this study, tape strips provide a minimally invasive alte...

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A minimally invasive tool to study immune response and skin barrier in children with atopic dermatitis

Cited by 59 publications

References 37 publications

Useful components in the stratum corneum for assessment of atopic dermatitis

Useful components in the stratum corneum for assessment of atopic dermatitis

Stripping Away Barriers to Find Relevant Skin Biomarkers for Pediatric Atopic Dermatitis

Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis

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