定义特应性皮炎发作和缓解过程中皮肤微生物组、免疫反应和皮肤屏障功能之间的时间关系：丹麦干预研究方案。

Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study.

机构信息

Department of Dermatology and Venerology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.

Department of Immunology and Microbiology, Costerton Biofilm Center, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark.

出版信息

BMJ Open. 2023 Feb 17;13(2):e068395. doi: 10.1136/bmjopen-2022-068395.

DOI:10.1136/bmjopen-2022-068395

PMID:36806068

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9944644/

Abstract

INTRODUCTION

Lesional skin of atopic dermatitis (AD) is often colonised by and the bacterial abundance increases during a flare. However, the role of and the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.

METHODS AND ANALYSIS

This clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologous , staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.

ETHICS AND DISSEMINATION

The scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov: NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.

TRIAL REGISTRATION NUMBER

NCT05578482, EudraCT 2021-006883-2.

摘要

简介

特应性皮炎（AD）的病灶皮肤常被定植，且在发作期间细菌丰度增加。然而，和皮肤微生物组在 AD 发病机制中的作用，包括其对功能失调的皮肤屏障和免疫反应的影响，仍有待阐明。在这项研究中，我们研究了成人 AD 患者的皮肤屏障功能、炎症和微生物组之间的时间关系。

方法和分析

本临床研究包括 81 名 Hanifin 和 Rajka 标准定义的成人 AD 患者和 41 名年龄和性别匹配的对照者。目的是在（1）未经治疗的 AD 发作、（2）AD 发作用局部皮质类固醇（TCS）治疗、（3）AD 发作用全身双氯西林/安慰剂和 TCS 治疗或（4）自身、葡萄球菌肠毒素 B 或载体局部暴露期间，研究皮肤微生物组、皮肤屏障和免疫反应的变化。采集皮肤活检、胶带条、皮肤和鼻拭子，使用 RNA 测序、多重免疫分析、液相色谱-质谱和 16S rDNA 进行分析。分析血液样本中的丝聚蛋白基因突变和白细胞基因表达。

伦理和传播

丹麦首都地区科学伦理委员会（第 I 阶段和第 II 阶段：H-20011047，第 III 阶段和第 IV 阶段：H-21079287）、当地数据保护局（第 I 阶段和第 II 阶段：P-2020-165，第 III 阶段和第 IV 阶段：P-2022-250）和丹麦药品管理局（第 III 阶段和第 IV 阶段：EudraCT 2021-006883-25，ClinicalTrials.gov：NCT05578482）已批准该研究。参与者将在研究开始前书面知情同意。该研究符合赫尔辛基宣言。结果将在国家和国际会议以及国际同行评议的出版物上公布。