Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis
Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis
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DOI：
10.1001/jamadermatol.2019.2983
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发表时间：
2019-12-01
期刊：
影响因子：
10.9
通讯作者：
Paller, Amy S.
中科院分区：
文献类型：
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作者：
Guttman-Yassky, Emma;Diaz, Aisleen;Paller, Amy S.
胶带条能否作为评估早发性儿童特应性皮炎生物标志物的微创方法？结果在这项横断面研究中，51名5岁以下的儿童患有和不患有特应性皮炎，使用胶带，皮肤采样的微创方法，检测婴儿和幼儿早发性特应性皮炎的皮肤免疫和屏障异常，并定义与疾病严重程度，瘙痒和经皮水分流失相关的生物标志物。意义微创胶带条可用于广泛表征免疫和表皮屏障生物标志物的病变和非病变皮肤的儿童早发性儿童特应性皮炎，提供了一个有用的，非侵入性的方法为儿科临床试验和纵向study.Importance皮肤活检的分子分析是评估皮肤特应性皮炎（AD）表型的标准。然而，皮肤活检并不总是可行的儿童。缺乏一种可重复的微创方法，可以在儿科纵向研究或临床试验中跟踪皮肤疾病。目的评估一种微创方法，使用胶带条来识别皮肤生物标志物，可以作为使用全组织活检识别的生物标志物的替代品。设计，设置，和参与者这项横断面研究的51名儿童年龄小于5岁的儿童中招募的儿童与中度至重度AD和儿童没有AD的皮肤科门诊在儿童医院。从2016年1月22日至2018年4月20日期间，从21名患有AD且距离疾病开始不到6个月的儿童的非病变和病变皮肤以及30名未患有AD的儿童的正常皮肤中连续收集了16条胶带。主要结果和指标采用实时定量聚合酶链反应和免疫组织化学方法评价基因和蛋白表达。结果51名5岁以下儿童纳入研究; 21名儿童患有中重度AD，病程少于6个月，30名儿童未患有AD。在21例AD儿童中，平均（SD）年龄为1.7（1.7）岁，大多数为男性（15例[71.4%]）和白色（15例[71.4%]）。在30例无AD的儿童中，平均（SD）年龄为1.8（2.0）岁，大多数为女性（20例[66.7%]）和白色（22例[73.3%]）。在71个胶带条中的70个（样品检测率，99%）中检测到79个评估的免疫和屏障基因产物中的77个（基因检测率，97%），其中79个标记物中的53个用于区分患有病变性和/或非病变性AD的儿童与没有AD的儿童。T细胞（CD 3）、AD相关树突状细胞的多种细胞标志物（Fc β RI和OX 40配体受体），以及关键的炎症（基质金属肽酶12），先天性（白细胞介素8 [IL-8]和IL-6）、辅助性T细胞2（T（H）2; IL-4、IL-13和趋化因子CCL 17和CCL 26）和T（H）17/T（H）22（IL-19、IL-36 G和S100 A蛋白）基因在有损伤和无损伤AD中与正常皮肤的胶带条相比显著增加。例如，病变的IL-4平均值（SE）为-15.2（0.91），正常为-19.5（0.48）; P < .001。表皮屏障基因产物（FLG、CLDN 23和FA 2 H）和负性免疫调节因子（IL-34和IL-37）也出现平行减少。例如，FLG病变的降低平均值（SE）为-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表皮水分丢失与T（H）2（IL-33和IL-4 R）和T（H）17/T（H）22（IL-36 G和S100 As）产品之间存在关联（使用特应性皮炎评分、湿疹面积和严重程度指数以及特应性皮炎瘙痒快速评分工具进行评估）。结论和相关性在这项研究中，胶带条为连续评估AD相关皮肤生物标志物提供了一种微创替代方法，并可能被证明可用于跟踪儿科AD治疗反应和预测未来病程和合并症。部分研究检查胶带是否可用于检测5岁以下儿童的免疫和屏障异常，并定义与特应性皮炎相关的生物标志物患有早发性特应性皮炎
Question Can tape strips serve as a minimally invasive approach to assess biomarkers for early-onset pediatric atopic dermatitis? Findings In this cross-sectional study of 51 children younger than 5 years with and without atopic dermatitis, the use of tape strips, a minimally invasive approach for skin sampling, detected the cutaneous immune and barrier abnormalities of early-onset atopic dermatitis in infants and young children and defined biomarkers that are associated with disease severity, pruritus, and transepidermal water loss. Meaning Minimally invasive tape strips can be used to broadly characterize immune and epidermal barrier biomarkers of the lesional and nonlesional skin of children with early-onset pediatric atopic dermatitis, providing a useful, noninvasive approach for pediatric clinical trials and longitudinal studies.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 epsilon RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (T(H)2; IL-4, IL-13, and chemokines CCL17 and CCL26), and T(H)17/T(H)22 (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 T(H)2 (IL-33 and IL-4R) and T(H)17/T(H)22 (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.This cross-sectional study examines whether tape strips might be used to detect immune and barrier abnormalities and to define biomarkers associated with atopic dermatitis in children younger than 5 years with early-onset atopic dermatitis.