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

Abstract

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...

Measurement of serum Interleukin 34 (IL‐34) and correlation with severity and pruritus scores in client‐owned dogs with atopic dermatitis

“…This has been evaluated in two human AD studies, although both lack assessment of serum IL-34 correlation with severity. 13,14 The correlation of disease severity and serum IL-34 is consistent with evidence from a range of human inflammatory conditions such as rheumatoid arthritis (RA), inflammatory bowel disease, cutaneous lupus and ischemic cardiomyopathy. 7,10 Human patients with RA showed evidence of IL-34 induction at early diagnosis with further elevations linked to chronicity.…”

“…[5][6][7][8][9][10][11] In these diseases, serum IL-34 concentrations were correlated with disease severity and high IL-34 was a poor prognostic marker. 12 Specific to skin diseases, IL-34 protein and gene expression was detected in both lesional, nonlesional and normal skin from adults and children with AD, 13,14 although no study has assessed serum IL-34 in these patients or looked at correlation with disease severity.…”

Tape-Strip Proteomic Profiling of Atopic Dermatitis on Dupilumab Identifies Minimally Invasive Biomarkers

“…This current study provides several novel findings. First, while tape-strips have been used to map the lesional and non-lesional AD cutaneous profiles at baseline ( 16 , 17 ), tape-strips have never been utilized to track molecular response to targeted treatment. Furthermore, the Olink proteomic assay, recently used to profile skin biopsies ( 28 ), has not yet been applied to analysis of tape-strips.…”

“…Tape-stripping, a minimally invasive approach that samples the stratum corneum and upper stratum granulosum (15,16), has been used to evaluate AD skin biomarkers, almost exclusively in untreated patients (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Koppes et al reported decreases in Th2 markers (e.g., IL-4, IL-13, CCL22) after local application of emollient to the skin (27).…”

Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: a systematic review for the EAACI Biologicals Guidelines

“…AD displays a highly complex pathophysiology and heterogeneous phenotypes, which are illustrated by different features such as age of disease onset, variable response to triggers, spectrum of severity, barrier defect, potential of IgE autoreactivity and comorbidities (asthma, rhinitis, food allergy and infections) (1,2,3,4,5,6). Similar to asthma, AD research is developing and shaping precision medicine approaches aiming towards a biomarker based molecular taxonomy (7,8,9,10).…”