Background

Monitoring the effects of biologic therapies in skin diseases will benefit from alternative noninvasive skin sampling techniques to evaluate immune pathways in diseased tissue early and longitudinally.

Objective

To establish a minimally invasive profiling of skin cytokines for diagnosis, therapeutic response monitoring, and clinical research in atopic dermatitis (AD) and other skin diseases, particularly in pediatric cohorts.

Methods

We developed a novel method for cytokine profiling in the epidermis using skin tape strips (STSs) in a setting designed to maximize the efficiency of protein extraction from STSs. This method was applied to analyze STS protein extracts from the lesional skin of children having AD (n = 41) and normal, healthy controls (n = 22). A total of 20 cytokines were probed with the ultrasensitive Mesoscale multiplex cytokine assay.

Results

A significant increase in interleukin (IL)-1b (P < .01), IL-18 (P < .001), and IL-8 (P < .001) with a decrease in IL-1a (P < .001) in the stratum corneum of AD lesional skin was found. Concurrently, an increase in markers associated with type 2 inflammatory response was readily detectable in AD lesional skin, including C-C motif chemokine ligand (CCL) 22, CCL 17, and thymic stromal lymphopoietin (TSLP). The levels of IL-1b, IL-18, and TSLP exhibited positive correlations with the AD severity index (Scoring AD index) and skin transepidermal water loss (TEWL), whereas an inverse correlation between IL-1a and Scoring AD index and IL-1a and TEWL was found. The levels of CCL17, CCL22, TSLP, IL-22, and IL-17a correlated with skin TEWL measurements.

Conclusion

Using minimally invasive STS analysis, we identified cytokine profiles easily sampled in AD lesional skin. The expression of these markers correlated with disease severity and reflected changes in TEWL in lesional skin. These markers suggest new response assessment targets for AD skin.

Trial Registration

ClinicalTrials.gov Identifier: NCT03168113.

中文翻译：

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皮肤胶带取样技术可鉴定特应性皮炎皮肤中的促炎细胞因子。

 背景

监测皮肤病生物疗法的效果将受益于替代性非侵入性皮肤采样技术，以早期和纵向评估患病组织中的免疫途径。

 客观的

建立皮肤细胞因子的微创分析，用于特应性皮炎（AD）和其他皮肤病（特别是儿科人群）的诊断、治疗反应监测和临床研究。

 方法

我们开发了一种使用皮肤胶带 (STS) 进行表皮细胞因子分析的新方法，其设计旨在最大限度地提高从 STS 中提取蛋白质的效率。该方法用于分析 AD 儿童 (n = 41) 和正常健康对照 (n = 22) 病变皮肤的 STS 蛋白提取物。使用超灵敏 Mesoscale 多重细胞因子测定法检测了总共 20 种细胞因子。

 结果

白介素 (IL)-1b ( P < .01)、IL-18 ( P < .001) 和 IL-8 ( P < .001) 显着增加，而 IL-1a 减少 ( P % 3C .001)在AD病变皮肤的角质层中被发现。同时，在 AD 皮损皮肤中很容易检测到与 2 型炎症反应相关的标志物的增加，包括 CC 基序趋化因子配体 (CCL) 22、CCL 17 和胸腺基质淋巴细胞生成素 (TSLP)。 IL-1b、IL-18和TSLP的水平与AD严重程度指数（AD评分指数）和皮肤经表皮失水量（TEWL）呈正相关，而IL-1a与AD指数和IL-1呈负相关。 1a 并发现 TEWL。 CCL17、CCL22、TSLP、IL-22 和 IL-17a 的水平与皮肤 TEWL 测量值相关。

 结论

使用微创 STS 分析，我们确定了在 AD 病变皮肤中轻松采样的细胞因子谱。这些标记物的表达与疾病严重程度相关，并反映了病变皮肤 TEWL 的变化。这些标记为 AD 皮肤提出了新的反应评估目标。

 试用注册

ClinicalTrials.gov 标识符：NCT03168113。