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

Daphne S. Bakker, Maria M. van der Wal, Lukas E.M. Heeb, Barbara Giovannone, Mindy Asamoah, Eveline M. Delemarre, Julia Drylewicz, Stefan Nierkens, Onur Boyman, Marjolein S. de Bruin-Weller, Judith L. Thijs, Femke van Wijk

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43 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1943-1953.e13
JournalJournal of Investigative Dermatology
Volume141
Issue number8
DOIs
Publication statusPublished - Aug 2021
Externally publishedYes

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