Complementary Analysis of Local and Systemic Effects of Dupilumab in Paediatric AD Using Tape Strips and Serum.

IF 6.3 2区 医学 Q1 ALLERGY
Lisa P van der Rijst, Edward F Knol, Nicolaas P A Zuithoff, Constance F den Hartog Jager, Femke van Wijk, Marjolein S de Bruin-Weller, Marlies de Graaf
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Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

使用胶带条和血清对Dupilumab治疗儿童AD的局部和全身效应进行补充分析。
目的:研究dupilumab治疗的儿童特应性皮炎(AD)患者胶带条和血清中局部和全身免疫相关蛋白,并探讨其与临床严重程度的相关性。结果:随着临床改善,16周的dupilumab治疗导致胶带剥离皮肤和血清中疾病相关介质PARC/CCL18和TARC/CCL17的快速和显著降低。虽然细胞因子和趋化因子谱在采样方法之间存在差异,但两者都有效地捕获了与杜匹单抗治疗相关的免疫变化。胶带条显示先天促炎细胞因子(IL-8/CXCL8, IL-18), T细胞募集趋化因子CTACK/CCL27, 1型免疫介质CXCL10和组织修复和重塑蛋白(骨膜蛋白,MMP-1)在治疗反应中显着降低,但在检测T细胞来源的细胞因子(IL-4, IL-13)方面不太敏感。在皮肤和血清中,通过EASI和NRS瘙痒测量,几种蛋白质与AD严重程度显著相关,其中PARC/CCL18是最强的相关蛋白。结论:我们的研究结果提供了对dupilumab治疗后儿科AD患者不同的局部和全身蛋白质组学变化的见解。这些发现强调了胶带条带和血清在分析免疫和表皮屏障蛋白方面的互补作用,强调了微创胶带条带用于监测儿科AD靶向治疗的蛋白质组学反应的实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.40
自引率
9.80%
发文量
189
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Allergy strikes an excellent balance between clinical and scientific articles and carries regular reviews and editorials written by leading authorities in their field. In response to the increasing number of quality submissions, since 1996 the journals size has increased by over 30%. Clinical & Experimental Allergy is essential reading for allergy practitioners and research scientists with an interest in allergic diseases and mechanisms. Truly international in appeal, Clinical & Experimental Allergy publishes clinical and experimental observations in disease in all fields of medicine in which allergic hypersensitivity plays a part.
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