Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ T helper 2 cells which may contribute to pruritus in lesional skin.

Autor:	Aala WJF; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Hou PC; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Hong YK; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan., Lin YC; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan., Lee YR; School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Tu WT; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan., Papanikolaou M; St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Benzian-Olsson N; St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Onoufriadis A; St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK.; Laboratory of Medical Biology and Genetics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece., I Chen Harn H; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Hwang DY; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan., Cheng SM; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan., Lu K; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Chen PC; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan., McGrath JA; School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; St John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Hsu CK; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
Jazyk:	angličtina
Zdroj:	The British journal of dermatology [Br J Dermatol] 2024 Jul 16; Vol. 191 (2), pp. 252-260.
DOI:	10.1093/bjd/ljae110
Abstrakt:	Background: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. Objectives: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. Methods: Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients. Results: The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment. Conclusions: Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus. Competing Interests: Conflicts of interest J.A.M. currently serves on the Editorial Advisory Board of BJD. The other authors declare no conflicts of interest. (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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