Regulated genes in psoriatic skin during treatment with fumaric acid esters

A. J. Onderdijk*, D. M. W. Balak, E. M. Baerveldt, E. F. Florencia, M. Kant, J. D. Laman, W. F. . J. van IJcken, E. Racz, D. de Ridder, H. B. Thio, E. P. Prens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BackgroundFumaric acid esters (FAEs) are widely used in Europe for the treatment of psoriasis because of their clinical efficacy and favourable safety profile. However, the mechanisms of action by which FAEs improve psoriasis remain largely unknown.

ObjectivesTo identify pathways and mechanisms affected by FAE treatment and to compare these with pathways affected by treatment with the antitumour necrosis factor (anti-TNF)- biologic etanercept.

MethodsIn a prospective cohort study, 50 patients with plaque psoriasis were treated with FAEs for 20weeks. Nine patients were randomly selected for gene expression profiling of plaque biopsies from week 0 and week 12. The groups consisted of FAE responders [>Psoriasis Area and Severity Index (PASI)-75 improvement] and nonresponders (

ResultsResponse to FAE treatment was associated with a2-fold change (P

ConclusionsFAE treatment induces glutathione and Nrf2 pathway genes in lesional skin of patients with psoriasis. In responders, FAEs specifically regulate the transcription factors PTTG1, NR3C1, GATA3 and NFBIZ, which are important in normal cutaneous development, and the T-helper (Th)2 and Th17 pathways, respectively.

What's already known about this topic?

Fumaric acid esters (FAEs) are used in the treatment of psoriasis, but the mechanisms of action are poorly known.In vitro actions of FAEs include inhibition of keratinocyte proliferation and inhibition of dendritic cell maturation.

What does this study add?

FAE treatment of patients with psoriasis specifically induces activation of the Nrf2 and glutathione pathways in psoriatic skin. GATA3 and NFBIZ are FAE-specific molecules related to treatment response and these transcription factors are important in the T-helper (Th)2 and Th17 pathways, respectively.

Original languageEnglish
Pages (from-to)732-741
Number of pages10
JournalBRITISH JOURNAL OF DERMATOLOGY
Volume171
Issue number4
DOIs
Publication statusPublished - Oct-2014

Keywords

  • PLACEBO-CONTROLLED PHASE-3
  • PROLACTIN-INDUCED PROTEIN
  • CHRONIC PLAQUE PSORIASIS
  • TO-SEVERE PSORIASIS
  • KAPPA-B-ZETA
  • MULTIPLE-SCLEROSIS
  • CELL-DIFFERENTIATION
  • DENDRITIC CELLS
  • LESIONAL SKIN
  • ORAL BG-12

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