Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape‐strips and biopsies

• Published in: Allergy (Copenhagen) Vol. 79; no. 1; pp. 80 - 92
• Main Authors: Del Duca, Ester, He, Helen, Liu, Ying, Pagan, Angel D., David, Eden, Cheng, Julia, Carroll, Britta, Renert‐Yuval, Yael, Bar, Jonathan, Estrada, Yeriel D., Maari, Catherine, Proulx, Etienne Saint‐Cyr, Krueger, James G., Bissonnette, Robert, Guttman‐Yassky, Emma
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.01.2024
• Subjects: Atopic dermatitis; biopsies; Biopsy; CD11c antigen; Clinical trials; Dendritic cells; Dermatitis; Dermatitis, Atopic - diagnosis; Dermatitis, Atopic - genetics; Eczema; Epidermis - pathology; gene expression regulation; Helper cells; Humans; Hyperplasia; immune; Innate immunity; interleukin-13; interleukin-8; Lymphocytes T; pain; pruritus; sequence analysis; Skin; Skin - pathology; Skin diseases; tape‐strips; Transcriptome; Transcriptomes; Transcriptomics; transient receptor potential vanilloid channels; Tumor necrosis factor; pruritus; atopic dermatitis; immune; biopsies; tape-strips
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.15845

Background Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape‐stripping is a minimally invasive, nonscarring technique to collect skin samples. Methods To construct a global AD skin transcriptomic profile comparing tape‐strips to whole‐skin biopsies, we performed RNA‐seq on tape‐strips and biopsies taken from the lesional skin of 20 moderate‐to‐severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold‐change (FCH) ≥2.0 and false discovery rate <0.05. Results We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape‐strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape‐strips showed higher FCHs for innate immunity (IL‐1B, IL‐8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL‐13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL‐22, S100As) and dermal cytokines (IFN‐γ, CCL26). Itch‐related genes (IL‐31, TRPV3) were preferentially captured by tape‐strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape‐strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. Conclusions Tape‐strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD‐related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies. This study presents a global RNA‐seq intrapatient profiling of tape‐strips and whole‐skin biopsies in moderate‐to‐severe AD as compared to healthy subjects. Although both techniques captured dysregulation of key immune genes, tape‐strips showed higher FCHs for innate immunity, dendritic cell, Th2, and Th17 products, while biopsies showed higher upregulation of Th22 associated genes and dermal cytokines. Itch‐related genes were preferentially captured by tape‐strips.Abbreviations: AD, atopic dermatitis; AKR1C3, aldo‐keto reductase family 1 member C3; ANXA, annexin; AOC1, amine oxidase copper containing 1; CAMP, cathelicidin antimicrobial peptide; CCL, C‐C motif chemokine ligand; CD, cluster of differentiation; CXCR, C‐X‐C motif chemokine receptor; CTLA4, cytotoxic T‐lymphocyte associated protein; DC, dendritic cell; DEGS2, delta 4‐desaturase, sphingolipid 2; ELOVL3, ELOVL fatty acid elongase 3; FA2H, fatty acid 2‐hydroxylase; FCER1A, Fc epsilon receptor 1A; FCH, fold chanage; FOXP3, forkhead box P3; GAL, galanin; GJPB, gap junction protein beta; GZMA, granzyme A; IL, interleukin; IL4RA, interleukin‐4 receptor alpha chain; IFNG, interferon gamma; ITG, integrin; ITK, IL‐2 inducible T cell kinase; KI67, marker of proliferation Ki‐67; KLK, kallikrein related peptidase; KRT6B, keratin 6B; LCN2, lipocalin 2; MX1, MX dynamin like GTPase 1; OASL, 2’‐5’‐oligoadenylate synthetase like; OSM, oncostatin M; PI3, peptidase inhibitor 3; OX40, TNF receptor superfamily member 4;  S100A, S100 calcium binding protein A; TRPM/V, transient receptor potential cation channel subfamily M/V member; XCL2, X‐C motif chemokine ligand 2