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Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris.

ABSTRACT: Psoriasis vulgaris is an inflammatory immune-mediated disease, with lesional skin characterized by sharply demarcated, erythematous scaly plaques. Uninvolved psoriatic skin appears clinically similar to normal skin. However, it has been hypothesized that inflammatory cytokines, e.g. interleukin (IL)-17, may affect any organ or tissue having a vascular supply; thus, distant uninvolved skin could be exposed to increased circulating IL-17.To establish comparative genomic profiles between noninvolved skin and normal skin, in particular, determining immune abnormalities in distant uninvolved skin.We performed a meta-analysis on three gene array studies, comparing the nonlesional (NL) psoriatic skin transcriptome with normal gene expression. We investigated immunological features of noninvolved skin, particularly linked to IL-17 signalling.We detected 252 differentially expressed gene transcripts in uninvolved skin compared with normal skin; multiple immune-related genes, including IL-17-downstream genes, were upregulated. Increased expression of IL-17-signature genes (e.g. DEFB4 and S100A7) was associated with an increased number of CD3+, CD8+ and DC-LAMP+ cells in NL skin vs. normal controls. Inducible T-cell costimulator (ICOS) expression was detected only in a few T-cells within NL skin.Our data described the genomic profile in NL skin, characterizing the immune activation that was mainly attributed to IL-17 signalling.

SUBMITTER: Chiricozzi A

PROVIDER: S-EPMC4720589 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris.

Chiricozzi A A Suárez-Fariñas M M Fuentes-Duculan J J Cueto I I Li K K Tian S S Brodmerkel C C Krueger J G JG

The British journal of dermatology 20151111 1

<h4>Background</h4>Psoriasis vulgaris is an inflammatory immune-mediated disease, with lesional skin characterized by sharply demarcated, erythematous scaly plaques. Uninvolved psoriatic skin appears clinically similar to normal skin. However, it has been hypothesized that inflammatory cytokines, e.g. interleukin (IL)-17, may affect any organ or tissue having a vascular supply; thus, distant uninvolved skin could be exposed to increased circulating IL-17.<h4>Objectives</h4>To establish comparati ...[more]

PMID: 26189551

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Project description:IntroductionNew generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited.ObjectivesTo compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis.MethodsA systematic review was undertaken to identify randomised controlled trials evaluating biologic treatments, apremilast and dimethyl fumarate. MEDLINE, MEDLINE In-Process, Embase and the Cochrane Library were searched from the 1st January 2000 to 22nd November 2018. A Bayesian network meta-analysis (NMA) using a random-effects multinomial likelihood model with probit link and meta-regression to adjust for cross-trial variation in placebo responses compared the efficacy of interventions at inducing different levels of Psoriasis Area and Severity Index (PASI) response during the induction period. A range of sensitivity analyses was undertaken.ResultsSeventy-seven trials (34,816 patients) were included in the NMA. The base-case analysis showed that all active treatments were superior to placebo. IL-17 inhibitors, guselkumab and risankizumab were found to be more efficacious than tildrakizumab, ustekinumab, all TNF inhibitors and non-biologic systemic treatments at inducing all levels of PASI response. In addition, brodalumab, ixekizumab and risankizumab were significantly more efficacious than secukinumab; no significant difference was found in the comparison with guselkumab. The greatest benefit of brodalumab, ixekizumab, guselkumab, and risankizumab was seen for PASI 90 and PASI 100 response. Results were consistent across all analyses.ConclusionsIn the NMA brodalumab, ixekizumab, risankizumab and guselkumab showed the highest levels of short-term efficacy. There were differences in efficacy between treatments within the same class. Longer-term analyses are needed to understand differences between these drugs beyond induction in what is a life-long condition.

Dataset Information

Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris.

Publications

Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris.

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