Early and Long-Term Effects of Dupilumab Treatment on Circulating T-Cell Functions in Patients with Moderate-to-Severe Atopic Dermatitis.

Autor:	Bakker DS; National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., van der Wal MM; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Heeb LEM; Department of Immunology, University Hospital Zurich, Zurich, Switzerland., Giovannone B; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Asamoah M; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Delemarre EM; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Drylewicz J; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Nierkens S; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., Boyman O; Department of Immunology, University Hospital Zurich, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland., de Bruin-Weller MS; National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands., Thijs JL; National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands., van Wijk F; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: F.vanWijk@umcutrecht.nl.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2021 Aug; Vol. 141 (8), pp. 1943-1953.e13. Date of Electronic Publication: 2021 Feb 18.
DOI:	10.1016/j.jid.2021.01.022
Abstrakt:	Dupilumab, a mAb targeting IL-4 receptor alpha (IL-4Rα), markedly improves disease severity in patients with atopic dermatitis. However, the effect of IL-4Rα blockade on dynamics of circulating skin-homing T cells, which are crucial players in the pathologic mechanism of atopic dermatitis, has not been studied yet. In addition, it remains unknown whether dupilumab treatment induces long-lasting T- and B-cell polarization. Therefore, we studied the short- and long-term effects of dupilumab treatment on IL-4Rα expression and T-cell cytokine production within total and skin-homing (cutaneous lymphocyte antigen + /CCR4 + ) subpopulations in patients with moderate-to-severe atopic dermatitis. Dupilumab treatment completely blocked IL-4Rα expression and signal transducer and activator of transcription 6 phosphorylation in CD19 + B cells and CD4 + T cells within 2 hours of administration and through week 52. Although no change in the proportion of skin-homing T-cell subsets was found, dupilumab treatment significantly decreased the percentage of proliferating (Ki67 + ) and T helper type 2 and T helper type 22 cytokine-producing skin-homing CD4 + T cells at week 4. No evidence of general T helper type cell skewing following a year of dupilumab treatment was found. In summary, dupilumab treatment rapidly and stably inhibited IL-4Rα, which was accompanied by a strong early functional immunological effect specifically on skin-homing T cells without affecting overall T helper type cell skewing in the long term. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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