Helen He1, Robert Bissonnette2, Jianni Wu3, Aisleen Diaz4, Etienne Saint-Cyr Proulx2, Catherine Maari2, Carolyn Jack2, Maudeline Louis2, Yeriel Estrada5, James G Krueger6, Ning Zhang5, Ana B Pavel5, Emma Guttman-Yassky7. 1. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY. 2. Innovaderm Research, Montreal, Quebec, Canada. 3. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY; State University of New York Downstate Medical Center, College of Medicine, New York, NY. 4. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Ponce Health Sciences University School of Medicine, Ponce, Puerto Rico. 5. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. 6. Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY. 7. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address: emma.guttman@mountsinai.org.
Abstract
BACKGROUND: Our current understanding of atopic dermatitis (AD) and psoriasis pathophysiology is largely derived from skin biopsy studies that cause scarring and may be impractical in large-scale clinical trials. Although tape strips show promise as a minimally invasive technique in these common diseases, a comprehensive molecular profiling characterizing and differentiating the 2 diseases in tape strips is unavailable. OBJECTIVE: Our aim was to construct a global transcriptome of tape strips from lesional and nonlesional skin of adults with moderate-to-severe AD and psoriasis. METHODS: A total of 20 tape strips were obtained from lesional and nonlesional skin of patients with AD and psoriasis and skin from controls (n = 20 each); the strips were subjected to RNA sequencing (RNA-seq), with quantitative RT-PCR validation of immune and barrier biomarkers. RESULTS: We detected RNA-seq profiles in 96 of 100 of samples (96%), with 4123 and 5390 genes differentially expressed in AD and psoriasis lesions versus in controls, respectively (fold change ≥ 2; false discovery rate [FDR] < 0.05). Nonlesional tape-stripped skin from patients with AD was more similar to lesional skin than to nonlesional skin of patients with psoriasis, which showed larger differentiation from lesions. AD and psoriasis tissues shared increases in levels of dendritic cell and T-cell markers (CD3, ITGAX/CD11c, and CD83), but AD tissues showed preferential TH2 skewing (IL-13, CCL17/TARC, and CCL18), whereas psoriasis was characterized by higher levels of expression of TH17-related (IL-17A/F and IL-36A/IL-36G), TH1-related (IFN-γ and CXCL9/CXCL10), and innate immunity-related (nitric oxide synthase 2/inducible nitric oxide synthase and IL-17C) products (FDR < 0.05). Terminal differentiation (FLG2 and LCE5A), tight junction (CLDN8), and lipid biosynthesis and metabolism (FA2H and ALOXE3) products were significantly downregulated in both AD and psoriasis (FDR < 0.05). Nitric oxide synthase 2/inducible nitric oxide synthase expression (determined by quantitative PCR) differentiated AD and psoriasis with 100% accuracy. CONCLUSION: RNA-seq tape strip profiling detected distinct immune and barrier signatures in lesional and nonlesional AD and psoriasis skin, suggesting their utility as a minimally invasive alternative to biopsies for detecting disease biomarkers.
BACKGROUND: Our current understanding of atopic dermatitis (AD) and psoriasis pathophysiology is largely derived from skin biopsy studies that cause scarring and may be impractical in large-scale clinical trials. Although tape strips show promise as a minimally invasive technique in these common diseases, a comprehensive molecular profiling characterizing and differentiating the 2 diseases in tape strips is unavailable. OBJECTIVE: Our aim was to construct a global transcriptome of tape strips from lesional and nonlesional skin of adults with moderate-to-severe AD and psoriasis. METHODS: A total of 20 tape strips were obtained from lesional and nonlesional skin of patients with AD and psoriasis and skin from controls (n = 20 each); the strips were subjected to RNA sequencing (RNA-seq), with quantitative RT-PCR validation of immune and barrier biomarkers. RESULTS: We detected RNA-seq profiles in 96 of 100 of samples (96%), with 4123 and 5390 genes differentially expressed in AD and psoriasis lesions versus in controls, respectively (fold change ≥ 2; false discovery rate [FDR] < 0.05). Nonlesional tape-stripped skin from patients with AD was more similar to lesional skin than to nonlesional skin of patients with psoriasis, which showed larger differentiation from lesions. AD and psoriasis tissues shared increases in levels of dendritic cell and T-cell markers (CD3, ITGAX/CD11c, and CD83), but AD tissues showed preferential TH2 skewing (IL-13, CCL17/TARC, and CCL18), whereas psoriasis was characterized by higher levels of expression of TH17-related (IL-17A/F and IL-36A/IL-36G), TH1-related (IFN-γ and CXCL9/CXCL10), and innate immunity-related (nitric oxide synthase 2/inducible nitric oxide synthase and IL-17C) products (FDR < 0.05). Terminal differentiation (FLG2 and LCE5A), tight junction (CLDN8), and lipid biosynthesis and metabolism (FA2H and ALOXE3) products were significantly downregulated in both AD and psoriasis (FDR < 0.05). Nitric oxide synthase 2/inducible nitric oxide synthase expression (determined by quantitative PCR) differentiated AD and psoriasis with 100% accuracy. CONCLUSION: RNA-seq tape strip profiling detected distinct immune and barrier signatures in lesional and nonlesional AD and psoriasis skin, suggesting their utility as a minimally invasive alternative to biopsies for detecting disease biomarkers.
Authors: Adrian Kobiela; Joanna E Frackowiak; Anna Biernacka; Lilit Hovhannisyan; Aleksandra E Bogucka; Kinga Panek; Argho Aninda Paul; Joanna Lukomska; Xinwen Wang; Eleni Giannoulatou; Aleksandra Krolicka; Jacek Zielinski; Milena Deptula; Michal Pikula; Susanne Gabrielsson; Graham S Ogg; Danuta Gutowska-Owsiak Journal: Front Immunol Date: 2022-06-09 Impact factor: 8.786
Authors: Mirjam J Schaap; Finola M Bruins; Xuehui He; Kadri Orro; Malou Peppelman; Piet E J van Erp; Elke M G J de Jong; Hans J P M Koenen; Ellen H van den Bogaard; Marieke M B Seyger Journal: Skin Pharmacol Physiol Date: 2021-05-20 Impact factor: 3.479