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利用微创真皮贴片和全转录组分析深入了解反向性色素性扁平苔藓

Insights into Lichen Planus Pigmentosus Inversus using Minimally Invasive Dermal Patch and Whole Transcriptome Analysis.

作者信息

Dickman Jacob, Howell Michael, Hoopes Robert, Wang Yipeng, Dickerson Tobin J, Bottomley Michael, Shamma H Nicholas, Rapp Christine M, Turner Matthew J, Rohan Craig A, Travers Jeffrey B

机构信息

Department of Pharmacology & Toxicology, Wright State University, Dayton Ohio.

Mindera Corporation, San Diego, California.

出版信息

J Clin Investig Dermatol. 2022;10(1). doi: 10.13188/2373-1044.1000077. Epub 2022 Apr 5.

Abstract

Lichen Planus Pigmentosus inversus (LPPi) is a rare interface and lichenoid dermatitis (ILD) and supposed variant of lichen planus (LP) that presents as well-demarcated brown to grey macules in flexural and intertriginous areas. LPPi is deemed 'inversus' because its anatomical distribution in skin folds is opposite that seen in lichen planus pigmentosus (LPP) whose pigmented lesions arise on sun-exposed skin. Biopsy is required for the clinical diagnosis of all ILDs. Though multiple clinically-oriented studies have reported differences between LPP, LPPi, and LP, few molecular studies have been performed. In this case study, 3 patients, 2 with LPPi and one with LP, provided samples using minimally invasive whole transcriptome analysis using a dermal biomarker patch. This study confirms the involvement of interferon signaling and T-cell activation in LPPi and suggests an expression profile distinct from LP. Specific genes significantly upregulated in LPPi vs LP include an intergenic splice variant of the primary pigmentation determining receptor in humans and dysregulation of genes essential for ceramide synthesis and construction of the cornified envelope. This work expands upon our knowledge of the pathogenesis of LPPi vs LP, and supports the potential use of this technology in the diagnostic clinical setting to mitigate the need for invasive procedures.

摘要

色素性扁平苔藓反向型(LPPi)是一种罕见的界面性苔藓样皮炎(ILD),被认为是扁平苔藓(LP)的一种变异型,表现为屈侧和间擦部位边界清晰的棕色至灰色斑疹。LPPi被称为“反向型”,是因为其在皮肤褶皱处的解剖分布与色素性扁平苔藓(LPP)相反,后者的色素沉着性损害出现在暴露于阳光下的皮肤。所有ILD的临床诊断都需要活检。尽管多项临床研究报告了LPP、LPPi和LP之间的差异,但很少有分子研究。在本病例研究中,3例患者,2例LPPi患者和1例LP患者,使用真皮生物标志物贴片通过微创全转录组分析提供样本。本研究证实了干扰素信号传导和T细胞激活与LPPi有关,并提示其表达谱与LP不同。与LP相比,LPPi中显著上调的特定基因包括人类主要色素沉着决定受体的基因间剪接变体以及神经酰胺合成和角质包膜构建所必需基因失调。这项工作扩展了我们对LPPi与LP发病机制的认识,并支持在诊断临床环境中使用该技术以减少侵入性操作的需求。

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