van der Rijst Lisa P, Knol Edward F, Zuithoff Nicolaas P A, den Hartog Jager Constance F, van Wijk Femke, de Bruin-Weller Marjolein S, de Graaf Marlies
Department of Dermatology and Allergology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Clin Exp Allergy. 2025 Jul;55(7):552-563. doi: 10.1111/cea.70082. Epub 2025 May 15.
This study investigates local and systemic immune-related proteins in tape strips and serum of paediatric atopic dermatitis (AD) patients treated with dupilumab, and explores their correlation with clinical severity.
Twenty paediatric AD patients (< 18 years) starting dupilumab treatment were included. Serum samples and tape strips from lesional and non-lesional skin were collected at baseline, 4 and 16 weeks of treatment. Fifteen pre-specified proteins were measured at each visit by Luminex multiplex immunoassay. Clinical severity outcome measures included the Eczema Area and Severity Index (EASI) and Numeric Rating Scale (NRS) itch. Statistical analyses included Wilcoxon signed-rank tests and Spearman correlations.
Along with clinical improvement, 16 weeks of dupilumab treatment resulted in a rapid and significant reduction in the disease-associated mediators PARC/CCL18 and TARC/CCL17 in both tape-stripped skin and serum. While the cytokine and chemokine profiles differed between the sampling methods, both effectively captured immunological changes associated with dupilumab treatment. Tape strips demonstrated significant reductions in innate pro-inflammatory cytokines (IL-8/CXCL8, IL-18), the T cell-recruiting chemokine CTACK/CCL27, the Type 1 immune mediator CXCL10, and tissue repair and remodelling proteins (periostin, MMP-1) in response to treatment, but were less sensitive in detecting T cell-derived cytokines (IL-4, IL-13). In both skin and serum, several proteins were significantly correlated with AD severity, as measured by EASI and NRS itch, with PARC/CCL18 emerging as the strongest correlated protein.
Our findings provide insight into the distinct local and systemic proteomic changes in response to dupilumab treatment in paediatric AD patients. These findings underscore the complementary roles of tape strips and serum in profiling immune and epidermal barrier proteins, highlighting the utility of minimally invasive tape stripping for monitoring proteomic responses to targeted therapies in paediatric AD.
本研究调查接受度普利尤单抗治疗的儿童特应性皮炎(AD)患者胶带剥离样本和血清中局部和全身免疫相关蛋白,并探讨它们与临床严重程度的相关性。
纳入20例开始接受度普利尤单抗治疗的儿童AD患者(<18岁)。在治疗基线、第4周和第16周收集血清样本以及来自皮损和非皮损皮肤的胶带剥离样本。每次访视时通过Luminex多重免疫测定法检测15种预先指定的蛋白。临床严重程度结局指标包括湿疹面积和严重程度指数(EASI)以及数字评定量表(NRS)瘙痒评分。统计分析包括Wilcoxon符号秩检验和Spearman相关性分析。
随着临床改善,度普利尤单抗治疗16周导致胶带剥离皮肤和血清中与疾病相关的介质PARC/CCL18和TARC/CCL17迅速且显著减少。虽然两种采样方法的细胞因子和趋化因子谱有所不同,但两者均有效捕捉到与度普利尤单抗治疗相关的免疫变化。胶带剥离样本显示,治疗后先天性促炎细胞因子(IL-8/CXCL8、IL-18)、T细胞募集趋化因子CTACK/CCL27、1型免疫介质CXCL10以及组织修复和重塑蛋白(骨膜蛋白、基质金属蛋白酶-1)显著减少,但在检测T细胞衍生的细胞因子(IL-4、IL-13)方面敏感性较低。在皮肤和血清中,几种蛋白与通过EASI和NRS瘙痒评分衡量的AD严重程度显著相关,其中PARC/CCL18是相关性最强的蛋白。
我们的研究结果揭示了儿童AD患者接受度普利尤单抗治疗后局部和全身蛋白质组的独特变化。这些发现强调了胶带剥离样本和血清在分析免疫和表皮屏障蛋白方面的互补作用,突出了微创胶带剥离在监测儿童AD靶向治疗蛋白质组反应中的实用性。