IL-4/IL-13 Inhibitors for Atopic Dermatitis Induce Psoriatic Rash Transcriptionally Close to Pustular Psoriasis
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.
Mots clés
AD
atopic dermatitis DEG
differentially expressed gene DI-Pso
dupilumab-induced psoriatic eruption DC
dendritic cell FDR
false discovery rate GPP
generalized pustular psoriasis GSEA
Gene Set Enrichment Analysis HC
healthy control IPA
Ingenuity Pathway Analysis KC
keratinocyte PSO
plaque psoriasis Th
T helper UR
upstream regulator
atopic dermatitis
DEG
differentially expressed gene
DI-Pso
dupilumab-induced psoriatic eruption
DC
dendritic cell
FDR
false discovery rate
GPP
generalized pustular psoriasis
GSEA
Gene Set Enrichment Analysis
HC
healthy control
IPA
Ingenuity Pathway Analysis
KC
keratinocyte
PSO
plaque psoriasis
Th
T helper
UR
AD