Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment.
Atopic dermatitis
IL-13
IL-17
IL-4
Staphylococcus aureus
barrier
cytotoxins
dupilumab
microbiome
type 2 immunity
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
07
11
2022
revised:
05
05
2023
accepted:
11
05
2023
pmc-release:
13
12
2024
medline:
7
11
2023
pubmed:
15
6
2023
entrez:
14
6
2023
Statut:
ppublish
Résumé
Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity. This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab. Participants (n = 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping. At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in T Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for T
Sections du résumé
BACKGROUND
Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity.
OBJECTIVES
This study characterized the changes in the host-microbial interface in subjects with AD following type 2 blockade with dupilumab.
METHODS
Participants (n = 71) with moderate-severe AD were enrolled in a randomized (dupilumab vs placebo; 2:1), double-blind study at Atopic Dermatitis Research Network centers. Bioassays were performed at multiple time points: S aureus and virulence factor quantification, 16s ribosomal RNA microbiome, serum biomarkers, skin transcriptomic analyses, and peripheral blood T-cell phenotyping.
RESULTS
At baseline, 100% of participants were S aureus colonized on the skin surface. Dupilumab treatment resulted in significant reductions in S aureus after only 3 days (compared to placebo), which was 11 days before clinical improvement. Participants with the greatest S aureus reductions had the best clinical outcomes, and these reductions correlated with reductions in serum CCL17 and disease severity. Reductions (10-fold) in S aureus cytotoxins (day 7), perturbations in T
CONCLUSIONS
Blockade of IL-4 and IL-13 signaling, very rapidly (day 3) reduces S aureus abundance in subjects with AD, and this reduction correlates with reductions in the type 2 biomarker, CCL17, and measures of AD severity (excluding itch). Immunoprofiling and/or transcriptomics suggest a role for T
Identifiants
pubmed: 37315812
pii: S0091-6749(23)00754-6
doi: 10.1016/j.jaci.2023.05.026
pmc: PMC10716365
mid: NIHMS1920179
pii:
doi:
Substances chimiques
dupilumab
420K487FSG
Antibodies, Monoclonal, Humanized
0
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1179-1195Subventions
Organisme : NIAID NIH HHS
ID : UM2 AI117870
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI152011
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI151958
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117673
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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