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使用胶带条检测早发性特应性皮炎儿童皮肤的免疫和屏障异常。

Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis.

机构信息

Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai Medical Center, New York, New York.

School of Medicine, Ponce Health Sciences University, Ponce, Puerto Rico.

出版信息

JAMA Dermatol. 2019 Dec 1;155(12):1358-1370. doi: 10.1001/jamadermatol.2019.2983.

DOI:10.1001/jamadermatol.2019.2983
PMID:31596431
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6802262/
Abstract

IMPORTANCE

Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking.

OBJECTIVE

To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children's hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018.

MAIN OUTCOMES AND MEASURES

Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry.

RESULTS

A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was -15.2 (0.91) and normal was -19.5 (0.48); P < .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) -2.9 (0.42) and for normal was 2.2 (0.45); P < .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools).

CONCLUSIONS AND RELEVANCE

In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.

摘要

重要性

皮肤活检的分子谱分析是评估皮肤特应性皮炎(AD)表型的标准。然而,在儿童中并非总是可行进行皮肤活检。缺乏一种可重复性的微创方法,该方法可以在儿科纵向研究或临床试验中跟踪皮肤疾病。

目的

评估一种使用胶带条的微创方法,该方法可以识别皮肤生物标志物,这些标志物可以作为全组织活检鉴定的生物标志物的替代物。

设计、地点和参与者:本研究为一项横断面研究,共纳入 51 名年龄小于 5 岁的儿童,这些儿童均患有中重度 AD 或无 AD,他们分别来自一家儿童医院的皮肤科门诊。从 21 名 AD 儿童(疾病起始不到 6 个月)的非病变和病变皮肤以及 30 名无 AD 儿童的正常皮肤中连续采集 16 个胶带条,这些儿童在 2016 年 1 月 22 日至 2018 年 4 月 20 日期间就诊。

主要结局和测量

使用实时定量聚合酶链反应和免疫组织化学评估基因和蛋白表达。

结果

共有 51 名年龄小于 5 岁的儿童入组本研究;21 名儿童患有中重度 AD,疾病持续时间不到 6 个月,30 名儿童无 AD。21 名 AD 儿童的平均(SD)年龄为 1.7(1.7)岁,大多数为男性(15[71.4%])和白人(15[71.4%])。30 名无 AD 儿童的平均(SD)年龄为 1.8(2.0)岁,大多数为女性(20[66.7%])和白人(22[73.3%])。在 71 个胶带条(样本检测率为 99%)中评估了 79 个免疫和屏障基因产物中的 77 个(基因检测率为 97%),其中 53 个标记物可将病变和/或非病变 AD 儿童与无 AD 儿童区分开来。许多 T 细胞的细胞标志物(CD3)、AD 相关树突状细胞(Fc ε RI 和 OX40 配体受体)以及关键的炎症(基质金属蛋白酶 12)、先天(白细胞介素 8 [IL-8]和白细胞介素 6)、辅助 T 细胞 2(TH2;白细胞介素 4、白细胞介素 13 和趋化因子 CCL17 和 CCL26)和 TH17/TH22(白细胞介素 19、白细胞介素 36G 和 S100 蛋白)基因在病变和非病变 AD 中显著增加与正常皮肤的胶带条相比。例如,病变部位的白细胞介素 4 的平均(SE)为-15.2(0.91),正常皮肤为-19.5(0.48);P<0.001。表皮屏障基因产物(FLG、CLDN23 和 FA2H)和负免疫调节剂(IL-34 和 IL-37)也出现平行下降。例如,FLG 病变的下降幅度为平均(SE)-2.9(0.42),正常为 2.2(0.45);P<0.001。在病变和非病变 AD 皮肤中发现疾病严重程度或经皮水分丢失与 TH2(白细胞介素 33 和白细胞介素 4R)和 TH17/TH22(白细胞介素 36G 和 S100As)产物之间存在关联(使用特应性皮炎评分、湿疹面积和严重程度指数和瘙痒特应性皮炎快速评分工具评估)。

结论和相关性

在本研究中,胶带条提供了一种评估 AD 相关皮肤生物标志物的微创替代方法,可能对跟踪儿科 AD 治疗反应和预测未来病程和合并症有用。