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

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

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利用微创皮肤斑块和全转录组分析深入了解扁平苔藓色素沉着症。
色素沉着性扁平苔藓(LPPi)是一种罕见的界面和苔藓样皮炎(ILD),应该是扁平苔藓(LP)的变异型,表现为挠曲区和三叉神经间区分界清楚的棕色至灰色斑丘疹。LPPi 被认为是 "变异型",因为它在皮肤褶皱处的解剖分布与色素沉着性扁平苔藓(LPP)相反,后者的色素病变发生在暴露于阳光的皮肤上。所有 ILD 的临床诊断都需要活组织检查。虽然多项以临床为导向的研究报告了 LPP、LPPi 和 LP 之间的差异,但很少进行分子研究。在本病例研究中,3 名患者(其中 2 人患有 LPPi,1 人患有 LP)提供了样本,使用皮肤生物标记贴片进行了微创全转录组分析。这项研究证实了干扰素信号转导和 T 细胞活化参与了 LPPi 的发病,并提出了有别于 LP 的表达谱。与 LP 相比,LPPi 中明显上调的特定基因包括人类主要色素决定受体的基因间剪接变体,以及神经酰胺合成和粟粒状包膜构建所必需的基因失调。这项研究拓展了我们对LPPi与LP发病机理的认识,并支持将这项技术用于临床诊断,以减少对侵入性程序的需求。
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