Spatial and Temporal Variation in the Skin Transcriptome of Atopic Dermatitis Assessed by 1.5 mm Mini Punch Biopsies

To obtain a detailed molecular understanding of both the temporal and spatial variation in atopic dermatitis (AD), we conducted a longitudinal case-control study, in which we followed a population, the Gentofte AD (GENAD) cohort, of mild-to-moderate AD patients and matched healthy controls for more than a year. By the use of 1.5 mm punch biopsies, we obtained 393 samples from lesional, non-lesional and healthy skin, from multiple anatomic regions at different time points for transcriptomic profiling. After quality control, 339 samples remained for further analysis. We envisage that the application of small biopsies, such as those introduced in this study, combined with omics technologies, will enable future skin research, in which multiple sampling from the same individual will give a more detailed, dynamic picture of how a disease fluctuates in time and space. 30 AD patients and 30 healthy, age- and gender-matched healthy controls (HC) were enrolled in the study. For AD patients, biopsy specimens (1.5 mm) were taken at two lesional (LS) and two non-lesional (NL) skin sites. For HC, two skin biopsies were taken, preferably from the upper inner arm. A subpopulation of patients with AD and HC continued in a longitudinal study, where skin biopsies were taken at 3, 6, 9 and 12 months after the baseline visit. In total, and after quality control, 339 samples were included for transcriptomic profiling.

为了深入解析特应性皮炎（atopic dermatitis, AD）的时空动态变化特征，我们开展了一项纵向病例对照研究，针对根措夫特特应性皮炎（Gentofte AD, GENAD）队列中的轻度至中度AD患者与匹配健康对照组成的人群，开展了为期一年以上的随访。本研究通过1.5mm穿刺活检取材，从不同解剖部位的病变皮肤、非病变皮肤及健康皮肤中获取了393份样本，用于不同时间点的转录组学分析。经质量控制后，剩余339份样本用于后续研究。我们认为，本研究采用的小型活检技术结合组学技术，将为未来皮肤疾病研究提供助力——通过对同一受试者进行多次采样，可更精准、动态地刻画疾病在时空维度上的波动规律。本研究共纳入30名AD患者与30名年龄、性别匹配的健康对照（healthy controls, HC）。对于AD患者，分别于2处病变皮肤（lesional skin, LS）与2处非病变皮肤（non-lesional skin, NL）采集1.5mm活检样本；对于健康对照，优选于上臂内侧采集2份皮肤活检样本。其中一部分AD患者与健康对照参与了纵向随访研究，分别于基线访视后3、6、9及12个月再次采集皮肤活检样本。最终经质量控制后，共纳入339份样本用于转录组学分析。