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Randomized Controlled Trial
. 2024 Nov;154(5):1333-1338.e4.
doi: 10.1016/j.jaci.2024.06.023. Epub 2024 Jul 20.

Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis

Margot E Starrenburg  1 , Manal Bel Imam  2 , Juan F Lopez  2 , Laura Buergi  2 , N Tan Nguyen  3 , Anouk E M Nouwen  3 , Nicolette J T Arends  4 , Peter J Caspers  3 , Mübeccel Akdis  2 , Suzanne G M A Pasmans  3 , Willem van de Veen  5
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Free article
Randomized Controlled Trial

Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis

Margot E Starrenburg et al. J Allergy Clin Immunol. 2024 Nov.
Free article

Abstract

Background: A preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, an mAb targeting the IL-4 receptor α (IL-4Rα) 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+CD23hiIL-4Rα+ type 2 memory B cells (MBC2s) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies.

Objective: We sought to assess the effects of dupilumab treatment in comparison with alternative therapies on the frequency of MBC2s and the correlation to total IgE levels in pediatric patients with AD.

Methods: Pediatric patients with AD, participating in an ongoing trial, underwent randomization into 3 treatment groups: dupilumab (n = 12), cyclosporine (n = 12), and topical treatment (n = 12). Plasma samples and PBMCs were collected at baseline (T0) and at 6 months after starting therapy (T6). Flow cytometry was used for PBMC phenotyping, and ELISA was used to assess total IgE levels in plasma.

Results: Our findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. In addition, a significant correlation was observed between MBC2s and total IgE levels.

Conclusions: Systemic blocking of the IL-4Rα subunit leads to a decrease in circulating MBC2 cells and total IgE levels in pediatric patients with AD. Our findings unveiled a novel mechanism through which dupilumab exerts its influence on the atopic signature.

Keywords: IL-4 signaling; IgE; MBC2; atopic dermatitis; cyclosporine; dupilumab; memory B cells.

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Conflict of interest statement

Disclosure statement This work was supported by a grant from ZonMw (grant no. 848101005 to S.P.), with the Netherlands Organisation for Health Research and Development as the collaborating sponsor; a grant from the Promedica Stiftung Chur, Switzerland (grant no. 1515/M to W.V.); and a research fellowship from the European Academy of Allergy & Clinical Immunology (to M.S.). The funding sources of this research had no involvement in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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