Dupilumab Inhibits Vascular Leakage of Blood Proteins Into Atopic Dermatitis Skin.
Atopic dermatitis
Blood
Dupilumab
Proteomics
Skin barrier
Journal
The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
02
12
2022
revised:
16
02
2023
accepted:
13
03
2023
medline:
9
5
2023
pubmed:
24
3
2023
entrez:
23
3
2023
Statut:
ppublish
Résumé
Atopic dermatitis (AD) skin lesions are associated with oozing, bleeding, and erythema. This suggests that AD is associated with vascular changes. Dupilumab is an antibody to the alpha subunit of IL-4 receptor that demonstrates strong efficacy in the treatment of AD. IL-4 is known to reduce the permeability barrier function of vascular endothelium. To examine the effects of dupilumab on vascular barrier function in AD skin. Using proteomic analysis, we evaluated the plasma protein composition in skin tapes of lesional and nonlesional skin of adults and adolescents with moderate to severe AD over the course of a 16-week treatment with dupilumab and compared those with matched healthy subjects. At baseline, 115 plasma proteins were detected in AD skin and globally increased (1.5-fold or greater) compared with healthy skin. Functionally, these proteins included immunoglobulins, proteins involved in the coagulation process, enzymes, protease inhibitors, transport proteins, acute-phase proteins, complement proteins, and other pleiotropic proteins. Noteworthy, fibrinogens, fibronectin, and heme-binding proteins haptoglobin and hemopexin were among the top proteins originating from plasma and were increased in AD lesional versus healthy skin at baseline (P < .0001). Dupilumab treatment resulted in significantly reduced levels of plasma proteins in AD skin (P < .0001), with most dropping to levels seen in healthy skin or no longer detectable at week 16. Inhibition of IL-4/IL-13 action by dupilumab significantly reduces the efflux of plasma proteins into AD skin. Several of these proteins, such as fibrinogens and fibronectin, are known to enhance Staphylococcus aureus colonization and are associated with AD skin severity.
Sections du résumé
BACKGROUND
Atopic dermatitis (AD) skin lesions are associated with oozing, bleeding, and erythema. This suggests that AD is associated with vascular changes. Dupilumab is an antibody to the alpha subunit of IL-4 receptor that demonstrates strong efficacy in the treatment of AD. IL-4 is known to reduce the permeability barrier function of vascular endothelium.
OBJECTIVE
To examine the effects of dupilumab on vascular barrier function in AD skin.
METHODS
Using proteomic analysis, we evaluated the plasma protein composition in skin tapes of lesional and nonlesional skin of adults and adolescents with moderate to severe AD over the course of a 16-week treatment with dupilumab and compared those with matched healthy subjects.
RESULTS
At baseline, 115 plasma proteins were detected in AD skin and globally increased (1.5-fold or greater) compared with healthy skin. Functionally, these proteins included immunoglobulins, proteins involved in the coagulation process, enzymes, protease inhibitors, transport proteins, acute-phase proteins, complement proteins, and other pleiotropic proteins. Noteworthy, fibrinogens, fibronectin, and heme-binding proteins haptoglobin and hemopexin were among the top proteins originating from plasma and were increased in AD lesional versus healthy skin at baseline (P < .0001). Dupilumab treatment resulted in significantly reduced levels of plasma proteins in AD skin (P < .0001), with most dropping to levels seen in healthy skin or no longer detectable at week 16.
CONCLUSIONS
Inhibition of IL-4/IL-13 action by dupilumab significantly reduces the efflux of plasma proteins into AD skin. Several of these proteins, such as fibrinogens and fibronectin, are known to enhance Staphylococcus aureus colonization and are associated with AD skin severity.
Identifiants
pubmed: 36958520
pii: S2213-2198(23)00304-5
doi: 10.1016/j.jaip.2023.03.020
pii:
doi:
Substances chimiques
dupilumab
420K487FSG
Fibronectins
0
Interleukin-4
207137-56-2
Antibodies, Monoclonal, Humanized
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1421-1428Informations de copyright
Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.