Frisoli Michael L, Ko Wei-Che C, Martinez Nuria, Afshari Khashayar, Wang Yuqing, Garber Manuel, Harris John E
Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
Department of Dermatology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA; Department of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA.
J Invest Dermatol. 2025 May;145(5):1117-1126.e14. doi: 10.1016/j.jid.2024.09.008. Epub 2024 Sep 26.
Allergic contact dermatitis (ACD) is a pruritic skin disease caused by environmental chemicals that induce cell-mediated skin inflammation within susceptible individuals. Irritant contact dermatitis (ICD) is caused by direct damage to the skin barrier by environmental insults. Diagnosis can be challenging because both types of contact dermatitis can appear similar by visual examination, and histopathological analysis does not reliably distinguish ACD from ICD. To discover specific biomarkers of ACD and ICD, we characterized the transcriptomic and proteomic changes that occur within the skin during each type of contact dermatitis. We induced ACD and ICD in healthy human volunteers and sampled skin using a nonscarring suction blister biopsy method that collects interstitial fluid and cellular infiltrate. Single-cell RNA sequencing analysis revealed that cell-specific transcriptome differences rather than cell-type proportions best distinguished ACD from ICD. Allergy-specific genes were associated with upregulation of IFNG, and cell signaling network analysis implicated several other genes such as IL4, despite their low expression levels. We validated transcriptomic differences with proteomic assays on blister fluid and trained a logistic regression model on skin interstitial fluid proteins that could distinguish ACD from ICD and healthy control skin with 93% sensitivity and 93% specificity.
变应性接触性皮炎（ACD）是一种瘙痒性皮肤病，由环境化学物质引起，这些化学物质在易感个体中诱发细胞介导的皮肤炎症。刺激性接触性皮炎（ICD）是由环境刺激对皮肤屏障的直接损害所致。诊断可能具有挑战性，因为通过视觉检查，这两种类型的接触性皮炎可能看起来相似，而且组织病理学分析无法可靠地区分ACD和ICD。为了发现ACD和ICD的特异性生物标志物，我们对每种类型的接触性皮炎期间皮肤内发生的转录组和蛋白质组变化进行了表征。我们在健康人类志愿者中诱导了ACD和ICD，并使用一种无瘢痕的负压水疱活检方法采集皮肤样本，该方法可收集组织间液和细胞浸润物。单细胞RNA测序分析表明，细胞特异性转录组差异而非细胞类型比例最能区分ACD和ICD。变应性特异性基因与IFNG的上调相关，细胞信号网络分析涉及其他几个基因，如IL4，尽管它们的表达水平较低。我们用疱液蛋白质组学检测验证了转录组差异，并在皮肤组织间液蛋白质上训练了一个逻辑回归模型，该模型能够以93%的灵敏度和93%的特异性区分ACD、ICD和健康对照皮肤。
