Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2-high atopic dermatitis disease endotype.
Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2-high atopic dermatitis disease endotype.
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DOI：
10.1016/j.jaci.2017.10.046
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Leung DYM
中科院分区：
文献类型：
--
作者：
Dyjack N;Goleva E;Rios C;Kim BE;Bin L;Taylor P;Bronchick C;Hall CF;Richers BN;Seibold MA;Leung DYM
皮肤活检的表达谱已经确定了特应性皮炎 (AD) 皮肤的分子特征。活检的侵入性阻碍了其在大型研究中用于定义个体水平 AD 病理生物学机制（内型）。确定微创皮肤胶带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。我们从成年白种人AD患者（18名男性，12名女性；年龄（平均值±SE）36.3±2.2岁）和健康对照（9名男性，16名女性；年龄（平均值±SE）34.8±2.2岁）中采集了非病变和病变皮肤胶带条和活检样本。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、皮肤活检的免疫染色和临床特征相关性。皮肤胶带表达谱与皮肤活检谱不同，并且更好地采样了表皮分化复杂基因。 29 个免疫和表皮相关基因 (FDR<5%) 的皮肤胶带表达将 AD 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 受试者表现出 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 的过度表达（log2FC 分别为 5.5、2.0、4.0 和 4.1），并且在 T 辅助细胞 2/树突状细胞激活的通路水平上。皮肤活检的表达和免疫染色均表明该 2 型高组富含表达高亲和力 IgE 受体 (FcεRI) 的炎症性 2 型倾斜树突细胞。根据 EASI 评分和病变覆盖的体表面积，2 型高内型组表现出更严重的疾病。非病变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。
Expression profiling of skin biopsies has established molecular features of the skin in atopic dermatitis (AD). Invasiveness of biopsies has prevented their use in defining individual level AD pathobiological mechanisms (endotypes) in large research studies. To determine if minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. We sampled non-lesional and lesional skin tape strips and biopsies from adult Caucasian subjects AD patients (18 males, 12 females; age (Mean±SE) 36.3±2.2 yrs) and healthy controls (9 males, 16 females; age (Mean±SE) 34.8±2.2 yrs). Ampliseq whole transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsies, and clinical trait correlations were performed. 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 (FDR<5%) separated AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of AD subjects exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes including overexpression of IL13, IL4R, CCL22, CCR4 (log2FC=5.5, 2.0, 4.0, and 4.1, respectively), and at a pathway level by T-helper 2/dendritic cell activation. Both expression and immunostaining of skin biopsies indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing the high affinity IgE receptor (FcεRI). The type 2-high endotype group exhibited more severe disease by both EASI score and body surface area covered by lesions. Minimally invasive expression profiling of non-lesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
DOI：
10.1016/j.jaci.2017.01.011
发表时间：
2017-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brunner PM;Guttman-Yassky E;Leung DY
通讯作者：
Leung DY
影响因子：
5.2
作者：
Hanifin, Ion M.;Reed, Michael L.
通讯作者：
Reed, Michael L.
影响因子：
32.4
作者：
Howell, MD;Gallo, RL;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
14.2
作者：
Leung, Donald Y. M.;Guttman-Yassky, Emma
通讯作者：
Guttman-Yassky, Emma