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

• DOI: 10.1016/j.jid.2022.10.015
• Publication Date: 2023-01-05T08:06:18Z
• Authors: Chloé Grolleau; Andreea Calugareanu; Sarah Demouche; Audrey Nosbaum; Delphine Staumont...; Hélène Aubert; Charles Cassius; Marie Jachiet; Anne Saussine; Martine Bagot; Hervé Bachelez; Maxime Battistella; Claire Hotz; Aurélie Du Thanh; Marie-Noëlle Crépy; David Bergerat; Marine Merandet; Rachel Onifarasoa...; Antonio Alberdi; Alexandre How-Kit; Jean-David Bouaziz; Hélène Le-Buanec
• Keywords: Pathogenesis; Interleukin-23

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 = 7) compared with those of plaque psoriasis, AD, and healthy controls (n = 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.