Background

Expression profiling of skin biopsy specimens has established molecular features of the skin in patients with atopic dermatitis (AD). The invasiveness of biopsies has prevented their use in defining individual-level AD pathobiological mechanisms (endotypes) in large research studies.

Objective

We sought to determine whether minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes.

Methods

We sampled nonlesional and lesional skin tape strips and biopsy specimens from white adult patients with AD (18 male and 12 female patients; age [mean ± SE], 36.3 ± 2.2 years) and healthy control subjects (9 male and 16 female subjects; age [mean ± SE], 34.8 ± 2.2 years). AmpliSeq whole-transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsy specimens, and clinical trait correlations were performed.

Results

Skin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (false discovery rate < 5%) separated patients with AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of patients with AD exhibited a type 2 inflammatory signature (type 2–high endotype) characterized by differential expression of 656 genes, including overexpression of IL13, IL4R, CCL22, CCR4 (log₂ fold change = 5.5, 2.0, 4.0, and 4.1, respectively) and at a pathway level by T_H2/dendritic cell activation. Both expression and immunostaining of skin biopsy specimens indicated this type 2–high group was enriched for inflammatory, type 2–skewed dendritic cells expressing FcεRI. The type 2–high endotype group exhibited more severe disease by using both the Eczema Area and Severity Index score and body surface area covered by lesions.

Conclusion

Minimally invasive expression profiling of nonlesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.

中文翻译：

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微创皮肤胶带条 RNA 测序确定 2 型高特应性皮炎疾病内型的新特征

背景

皮肤活检标本的表达谱已经确定了特应性皮炎 (AD) 患者皮肤的分子特征。活检的侵入性阻止了它们在大型研究中定义个体水平的 AD 病理生物学机制（内型）。

客观的

我们试图确定微创皮肤胶带条转录组分析是否可以识别 AD 和分子疾病内型中的基因表达失调。

方法

我们从患有 AD 的白人成年患者（18 名男性和 12 名女性患者；年龄 [平均值 ± SE]，36.3 ± 2.2 岁）和健康对照受试者（9 名男性和 16 名女性受试者；年龄[平均值 ± SE]，34.8 ± 2.2 年）。对提取的 RNA 进行 AmpliSeq 全转录组测序。进行了差异表达、聚类/通路分析、皮肤活检标本的免疫染色和临床特征相关性。

结果

皮肤胶带表达谱不同于皮肤活检谱和更好的表皮分化复合基因采样。29 个免疫和表皮相关基因的皮肤胶带表达（错误发现率 < 5%）将 AD 患者与健康受试者区分开来。不可知基因集分析和聚类显示 50% 的 AD 患者表现出 2 型炎症特征（2 型高内型），其特征是 656 个基因的差异表达，包括IL13、IL4R、CCL22、CCR4的过表达（log ₂倍变化 = 5.5, 2.0, 4.0, 和 4.1，分别）和 T _H的通路水平2/树突状细胞活化。皮肤活检标本的表达和免疫染色均表明该 2 型高组富含表达 FcεRI 的炎性、2 型倾斜树突状细胞。通过使用湿疹面积和严重性指数评分以及病变覆盖的体表面积，2 型高内型组表现出更严重的疾病。

结论

非损伤性皮肤的微创表达谱揭示了 AD 分子病理学中与疾病严重程度相关的 2 型炎症的分层。