Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis - 09/01/21
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.
Il testo completo di questo articolo è disponibile in PDF.Graphical abstract |
Key words : Atopic dermatitis, psoriasis, tape strips, biomarker, skin, RNA sequencing, TH1, TH2, TH17, immune, epidermal barrier
Abbreviations used : AD, AUC, CCL, CXCL, DC, DEG, FCH, FDR, IGA, iNOS, LCE, NOS, PGA, qRT-PCR, RNA-seq, TLSS, TSS
Mappa
| Disclosure of potential conflict of interest: J. G. Krueger is an employee of the Rockefeller University and has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to her institution) from AbbVie, Celgene, Eli Lilly, Janssen, Medimmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB. E. Guttman-Yassky is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. R. Bissonnette is an advisory board member, consultant, speaker, and/or investigator for and/or receives honoraria or grant from AbbVie, AntibioTx, Aquinox Pharma, Arcutis, Arena Pharma, Asana BioSciences, Bellus Health, Boehringer-Ingelheim, Brickell Biotech, Dermavant, Celgene, Dignity Sciences, Eli Lilly, EMD Serono, Galderma, Glenmark, GSK-Stiefel, Incyte, Kiniksa, Leo Pharma, Neokera, Novan, Pfizer, Ralexar, Regeneron Pharmaceuticals, Sanofi Genzyme, Sienna, and Vitae. R. Bissonnette is also an employee and shareholder of Innovaderm Research. E. Saint-Cyr Proulx is an advisory board member, consultant, speaker, and/or investigator for and/or receives honoraria or grant from AbbVie, AntibioTx, Arcutis, Asana BioSciences, Bellus Health, Boehringer-Ingelheim, Brickell Biotech, Dermavant, Celgene, Eli Lilly, Galderma, Glenmark, GSK-Stiefel, Incyte, Kiniksa, Leo Pharma, Neokera, Pfizer, Ralexar, Regeneron Pharmaceuticals, Sanofi Genzyme, Sienna, UCB, and Vitae. Y. Estrada, N. Zhang, and A. B. Pavel are employees of Mount Sinai. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 1
P. 199-212 - Gennaio 2021 Ritorno al numero
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