IL-4/IL-13 Inhibitors for Atopic Dermatitis Induce Psoriatic Rash Transcriptionally Close to Pustular Psoriasis - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Journal of Investigative Dermatology Année : 2023

IL-4/IL-13 Inhibitors for Atopic Dermatitis Induce Psoriatic Rash Transcriptionally Close to Pustular Psoriasis

Audrey Nosbaum
Maxime Battistella
Claire Hotz
Aurélie Du Thanh
Rachel Onifarasoaniaina
Alexandre How-Kit

Résumé

Dupilumab is a therapeutic antibody targeting IL-4 and IL-13 receptor subunit alpha used for the treatment of patients with atopic dermatitis (AD). Cases of psoriasis-like reactions induced under dupilumab treatment (dupilumab-induced psoriatic eruption [DI-Pso]) for AD were recently reported. To understand the pathogenesis of DI-Pso, we performed gene expression profiling studies on skin biopsies of DI-Pso (n ¼ 7) compared with those of plaque psoriasis, AD, and healthy controls (n ¼ 4 each). Differential gene expression was performed using enrichment and Gene Ontology analysis. Gene expression was validated by qPCR, and protein levels were assessed by immunohistochemistry. Transcriptomic and protein analysis of DI-Pso compared with that of healthy controls, plaque psoriasis, and AD skins revealed activation of T helper 17/IL-23 pathways associated with a significant expression of IL-36, surrogate marker of pustular psoriasis. By contrast, T helper 2 representative genes' expression was strongly decreased in DI-Pso across comparison. Matching analysis with public data of pustular psoriasis skin corroborated that DI-Pso and pustular psoriasis upstream regulators overlap, greater than the overlap with plaque psoriasis. Furthermore, DI-Pso showed strongly decreased expression of many barrier skin genes compared with healthy controls, plaque psoriasis, and AD. Our data indicate that the pathogenesis of DI-Pso relied on a shift of skin immune responses from a T helper 2 to an IL-36 and T helper 17 polarization and on intensified skin barrier alterations.
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inserm-04311288 , version 1 (28-11-2023)

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Chloé Grolleau, Andreea Calugareanu, Sarah Demouche, Audrey Nosbaum, Delphine Staumont-Sallé, et al.. IL-4/IL-13 Inhibitors for Atopic Dermatitis Induce Psoriatic Rash Transcriptionally Close to Pustular Psoriasis. Journal of Investigative Dermatology, 2023, 143 (5), pp.711-721.e7. ⟨10.1016/j.jid.2022.10.015⟩. ⟨inserm-04311288⟩
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