Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
J Allergy Clin Immunol. 2015 Nov;136(5):1277-87. doi: 10.1016/j.jaci.2015.06.032. Epub 2015 Aug 24.
Alopecia areata (AA) is a common T cell-mediated disorder with limited therapeutics. A molecular profile of cytokine pathways in AA tissues is lacking. Although studies have focused on TH1/IFN-γ responses, several observations support a shared genetic background between AA and atopy.
We sought to define the AA scalp transcriptome and associated biomarkers with comparisons with atopic dermatitis (AD) and psoriasis.
We performed microarray and RT-PCR profiling of 27 lesional and 17 nonlesional scalp samples from patients with AA for comparison with normal scalp samples (n = 6). AA gene expression was also compared with samples from patients with lesional or nonlesional AD and those with psoriasis. A fold change of greater than 1.5 and a false discovery rate of less than 0.05 were used for differentially expressed genes (DEGs).
We established the AA transcriptomes (lesional vs nonlesional: 734 DEGs [297 upregulated and 437 downregulated]; lesional vs normal: 4230 DEGs [1980 upregulated and 2250 downregulated]), including many upregulated immune and downregulated hair keratin genes. Equally impressive as upregulation in TH1/interferon markers (IFNG and CXCL10/CXCL9) were those noted in TH2 (IL13, CCL18, CCL26, thymic stromal lymphopoietin, and periostin), TH9/IL-9, IL-23 (p40 and p19), and IL-16 mediators (all P < .05). There were no increases in TH17/TH22 markers. Hair keratin (KRT) expressions (ie, KRT86 and KRT85) were significantly suppressed in lesional skin. Greater scalp involvement (>25%) was associated with greater immune and keratin dysregulation and larger abnormalities in nonlesional scalp samples (ie, CXCL10 and KRT85).
Our data associate the AA signature with TH2, TH1, IL-23, and IL-9/TH9 cytokine activation, suggesting consideration of anti-TH2, anti-TH1, and anti-IL-23 targeting strategies. Similar to psoriasis and AD, clinical trials with selective antagonists are required to dissect key pathogenic pathways.
斑秃（AA）是一种常见的 T 细胞介导的疾病，治疗方法有限。AA 组织中细胞因子途径的分子谱尚不清楚。尽管研究集中在 TH1/IFN-γ 反应上，但有几个观察结果支持 AA 和特应性皮炎（AD）之间存在共同的遗传背景。
我们试图确定 AA 头皮转录组，并与 AD 和银屑病进行比较，以确定相关的生物标志物。
我们对 27 例活动性和 17 例非活动性 AA 患者的头皮样本进行了微阵列和 RT-PCR 分析，并与正常头皮样本（n=6）进行了比较。AA 基因表达也与 AD 患者的活动性或非活动性皮损和银屑病患者的样本进行了比较。差异表达基因（DEGs）的使用标准为倍数变化大于 1.5 和错误发现率（FDR）小于 0.05。
我们建立了 AA 转录组（活动性 vs 非活动性：734 个 DEGs [297 个上调和 437 个下调]；活动性 vs 正常：4230 个 DEGs [1980 个上调和 2250 个下调]），包括许多上调的免疫和下调的头发角蛋白基因。TH1/干扰素标志物（IFNG 和 CXCL10/CXCL9）的上调同样令人印象深刻，TH2（IL13、CCL18、CCL26、胸腺基质淋巴生成素和骨膜蛋白）、TH9/IL-9、IL-23（p40 和 p19）和 IL-16 介质（均 P <.05）也上调。TH17/TH22 标志物没有增加。角质蛋白（KRT）表达（即 KRT86 和 KRT85）在活动性皮肤中显著下调。头皮受累程度大于 25%（即，>25%）与免疫和角蛋白失调更大以及非活动性头皮样本中更大的异常（即，CXCL10 和 KRT85）相关。
我们的数据将 AA 特征与 TH2、TH1、IL-23 和 IL-9/TH9 细胞因子激活相关联，表明考虑采用抗 TH2、抗 TH1 和抗 IL-23 靶向策略。与银屑病和 AD 类似，需要进行选择性拮抗剂的临床试验来剖析关键的致病途径。
