TY - JOUR
T1 - Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis
T2 - protocol of a Danish intervention study
AU - Rønnstad, Amalie Thorsti Møller
AU - Bay, Lene
AU - Ruge, Iben Frier
AU - Halling, Anne-Sofie
AU - Fritz, Blaine Gabriel
AU - Jakaša, Ivone
AU - Luiten, Rosalie
AU - Kezic, Sanja
AU - Thomsen, Simon Francis
AU - Bjarnsholt, Thomas
AU - Thyssen, Jacob P
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - INTRODUCTION: Lesional skin of atopic dermatitis (AD) is often colonised by
Staphylococcus aureus and the bacterial abundance increases during a flare. However, the role of
S. aureus 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
S. aureus, 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.
AB - INTRODUCTION: Lesional skin of atopic dermatitis (AD) is often colonised by
Staphylococcus aureus and the bacterial abundance increases during a flare. However, the role of
S. aureus 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
S. aureus, 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.
KW - Adult
KW - Humans
KW - Dermatitis, Atopic/drug therapy
KW - Staphylococcus aureus
KW - Skin
KW - Immunity
KW - Denmark
U2 - 10.1136/bmjopen-2022-068395
DO - 10.1136/bmjopen-2022-068395
M3 - Journal article
C2 - 36806068
VL - 13
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 2
M1 - e068395
ER -