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日常实践中非侵入性皮肤生物标志物测量的挑战:经皮分析贴剂在儿童银屑病中检测皮肤表面蛋白的纵向研究。

Challenges in Noninvasive Skin Biomarker Measurements in Daily Practice: A Longitudinal Study on Skin Surface Protein Detection by the Transdermal Analysis Patch in Pediatric Psoriasis.

机构信息

Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.

FibroTx LLC, Tallinn, Estonia.

出版信息

Skin Pharmacol Physiol. 2022;35(6):319-327. doi: 10.1159/000527258. Epub 2022 Oct 6.

Abstract

INTRODUCTION

Skin surface proteins are potential biomarkers in psoriasis and can be measured noninvasively with the transdermal analysis patch (TAP). This study aimed to assess markers measured by TAP over time in daily clinical practice, explore their correlation with disease severity in pediatric psoriasis, and compare the TAP and tape stripping detection capability.

METHODS

In this prospective observational daily clinical practice study, pediatric psoriasis patients (aged >5 to <18 years) were followed during 1 year. At each visit, TAPs were applied to lesional (n = 2), peri-lesional (n = 2), and non-lesional (n = 1) sites. Post-lesional skin was sampled if all lesions on the arms, legs, or trunk cleared. Treatment and psoriasis severity data were collected. IL-1RA, hBD-2, IL-1α, IL-8, VEGF, CXCL-1/2, CCL-27, IL-23, hBD-1, IL-22, IL-17A, KLK-5, and IL-4 levels were quantified by spot-ELISA. For the statistical analysis, Wilcoxon signed rank tests, Mann-Whitney U tests, and Spearman correlations were used. Detection capability of the TAP was compared to tape stripping in a separate cohort of adult psoriasis patients.

RESULTS

32 patients (median age 15.0 years, median Psoriasis Area and Severity Index [PASI] 5.2) were followed for a mean of 11.3 (±3.4) months with a total of 104 visits. In lesional skin (n = 197), significantly higher IL-1RA, hBD-2, IL-8, VEGF, CXCL-1/2, IL-23, hBD-1, IL-22, CCL-27, and IL-17A levels were found compared to non-lesional skin (n = 104), while IL-1α was higher in non-lesional skin. Marker levels were highly variable over time and did not correlate with disease severity measured by PASI or SUM scores. Comparison of the TAP and tape strip detection capability in adult psoriasis patients (n = 10) showed that lesional hBD-2, IL1-α, IL-8, and VEGF and non-lesional IL-1RA, hBD-2, IL-8, and VEGF were more frequently detected in tape extracts than TAPs.

CONCLUSION

Due to the lack of correlation with clinical disease severity and the current detection capability of the markers measured by TAP in psoriasis, its use in regular practice is still a bridge too far.

摘要

简介

皮肤表面蛋白是银屑病潜在的生物标志物,可通过经皮分析贴剂(TAP)进行无创测量。本研究旨在评估 TAP 在日常临床实践中的长期测量标志物,探讨其与儿童银屑病严重程度的相关性,并比较 TAP 和胶带剥离检测能力。

方法

本前瞻性观察性日常临床实践研究纳入了年龄>5 岁至<18 岁的儿童银屑病患者,随访 1 年。每次就诊时,在皮损处(n=2)、皮损周围(n=2)和非皮损处(n=1)应用 TAP。如果手臂、腿部或躯干上的所有皮损均清除,则对皮损后的皮肤进行取样。收集治疗和银屑病严重程度数据。采用斑点 ELISA 定量检测 IL-1RA、hBD-2、IL-1α、IL-8、VEGF、CXCL-1/2、CCL-27、IL-23、hBD-1、IL-22、IL-17A、KLK-5 和 IL-4 水平。统计分析采用 Wilcoxon 符号秩检验、Mann-Whitney U 检验和 Spearman 相关性检验。在另一组成人银屑病患者中比较了 TAP 和胶带剥离的检测能力。

结果

32 名患者(中位年龄 15.0 岁,中位银屑病面积和严重程度指数[PASI]5.2)接受了平均 11.3(±3.4)个月的随访,共进行了 104 次就诊。在皮损处皮肤(n=197)中,与非皮损处皮肤(n=104)相比,发现 IL-1RA、hBD-2、IL-8、VEGF、CXCL-1/2、IL-23、hBD-1、IL-22、CCL-27 和 IL-17A 水平显著升高,而 IL-1α 水平在非皮损处皮肤升高。标志物水平随时间变化高度可变,与 PASI 或 SUM 评分测量的疾病严重程度无相关性。在成人银屑病患者(n=10)中比较 TAP 和胶带条检测能力的结果显示,皮损处 hBD-2、IL1-α、IL-8 和 VEGF 以及非皮损处 IL-1RA、hBD-2、IL-8 和 VEGF 在胶带提取物中比 TAP 更频繁地被检测到。

结论

由于缺乏与临床疾病严重程度的相关性,以及 TAP 测量的标志物目前的检测能力,其在常规实践中的应用仍遥遥无期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dadc/9811417/76bea843632b/spp-0035-0319-g01.jpg

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