Details

Autor(en) / Beteiligte

• Grolleau, Chloé
• Calugareanu, Andreea
• Demouche, Sarah
• Nosbaum, Audrey
• Staumont-Sallé, Delphine
• Aubert, Hélène
• Cassius, Charles
• Jachiet, Marie
• Saussine, Anne
• Bagot, Martine
• Bachelez, Hervé
• Battistella, Maxime
• Hotz, Claire
• Du Thanh, Aurélie
• Crépy, Marie-Noëlle
• Bergerat, David
• Merandet, Marine
• Onifarasoaniaina, Rachel
• Alberdi, Antonio
• How-Kit, Alexandre
• Bouaziz, Jean-David
• Le-Buanec, Hélène

Titel

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

Ist Teil von

• Journal of investigative dermatology, 2023-05, Vol.143 (5), p.711-721.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.