"Dupilumab Treatment Decreases MBC2s, Correlating with Reduced IgE Levels in Pediatric AD".

Atopic Dermatitis IL-4 signaling IgE MBC2 cyclosporine dupilumab memory B-cells

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:
20 Jul 2024
Historique:
received: 07 03 2024
revised: 23 05 2024
accepted: 13 06 2024
medline: 23 7 2024
pubmed: 23 7 2024
entrez: 22 7 2024
Statut: aheadofprint

Résumé

A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, a monoclonal antibody targeting the IL-4α receptor subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B-cells, critical in atopic diseases. Recent studies indicate IgG+CD23 To assess the effects of dupilumab treatment in comparison to alternative therapies on the frequency of MBC2 and the correlation to total IgE levels in pediatric patients with AD. Pediatric patients with AD, participating in an ongoing trial, underwent randomization into three treatment groups: dupilumab (n=12), cyclosporine (n=12), or topical treatment (n=12). Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were collected at baseline (T0) and after 6 months (T6). Flow cytometry was employed for PBMC phenotyping, ELISA was utilized to assess total IgE levels in plasma. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org RESULTS: Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. Additionally, a significant correlation was observed between MBC2s and total IgE levels CONCLUSION: Systemic blocking of the IL-4RA subunit leads to a decrease in circulating MBC2 cells and total IgE in pediatric AD patients. Our findings unveil a novel mechanism through which dupilumab exerts its influence on the atopic signature.

Sections du résumé

BACKGROUND BACKGROUND
A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, a monoclonal antibody targeting the IL-4α receptor subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B-cells, critical in atopic diseases. Recent studies indicate IgG+CD23
OBJECTIVE OBJECTIVE
To assess the effects of dupilumab treatment in comparison to alternative therapies on the frequency of MBC2 and the correlation to total IgE levels in pediatric patients with AD.
METHODS METHODS
Pediatric patients with AD, participating in an ongoing trial, underwent randomization into three treatment groups: dupilumab (n=12), cyclosporine (n=12), or topical treatment (n=12). Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were collected at baseline (T0) and after 6 months (T6). Flow cytometry was employed for PBMC phenotyping, ELISA was utilized to assess total IgE levels in plasma. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org RESULTS: Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. Additionally, a significant correlation was observed between MBC2s and total IgE levels CONCLUSION: Systemic blocking of the IL-4RA subunit leads to a decrease in circulating MBC2 cells and total IgE in pediatric AD patients. Our findings unveil a novel mechanism through which dupilumab exerts its influence on the atopic signature.

Identifiants

pubmed: 39038586
pii: S0091-6749(24)00736-X
doi: 10.1016/j.jaci.2024.06.023
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Margot E Starrenburg (ME)

Center of Pediatric Dermatology-department of Dermatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Manal Bel Imam (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Juan F Lopez (JF)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Laura Buergi (L)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

N Tan Nguyen (NT)

Center of Pediatric Dermatology-department of Dermatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.

Anouk E M Nouwen (AEM)

Center of Pediatric Dermatology-department of Dermatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.

Nicolette J T Arends (NJT)

Center of Pediatric Allergology-department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.

Peter J Caspers (PJ)

Center of Pediatric Dermatology-department of Dermatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.

Mübeccel Akdis (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Suzanne G M A Pasmans (SGMA)

Center of Pediatric Dermatology-department of Dermatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.

Willem van de Veen (W)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. Electronic address: willem.vandeveen@siaf.uzh.ch.

Classifications MeSH