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

JAMA Dermatol. 2019 Dec 1;155(12):1358-1370. doi: 10.1001/jamadermatol.2019.2983.

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 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (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 TH2 (IL-33 and IL-4R) and TH17/TH22 (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 alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Biopsy / methods
  • Child, Preschool
  • Cross-Sectional Studies
  • Dermatitis, Atopic / diagnosis*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Feasibility Studies
  • Female
  • Filaggrin Proteins
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Male
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index
  • Skin / immunology
  • Skin / pathology*
  • Water Loss, Insensible / immunology

Substances

  • Biomarkers
  • FLG protein, human
  • Filaggrin Proteins