Project description:A gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin. Skin biopsy samples (n=170) were collected at baseline for RNA extraction and microarray analysis from 85 patients with moderate-to-severe psoriasis without receiving active psoriasis therapy.
Project description:A gene expression profiling study was conducted in which skin biopsy samples were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in the phase 1, guselkumab first-in-human randomized, double-blind, placebo-controlled trial. At week 12, significant reductions in psoriasis gene expression were observed in guselkumab-treated patients. Skin biopsy samples (n=59, LS: lesion, NL: non-lesion) were collected at baseline, weeks 1 and 12 following guselkumab treatment from patients with moderate-to-severe psoriasis for RNA extraction and microarray analysis.
Project description:A gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin.
Project description:A gene expression profiling study was conducted in which skin biopsy samples were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in the phase 1, guselkumab first-in-human randomized, double-blind, placebo-controlled trial. At week 12, significant reductions in psoriasis gene expression were observed in guselkumab-treated patients.
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Project description:A gene expression profiling sub-study was conducted in which skin biopsy samples (n=192) were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified gene expressions significantly modulated in psoriasis lesions (LS) following ustekinumab or etanercept treatment at week 12 compared to baseline. Molecular expression of mRNA was found to be different in ustekinumab PASI75 responders vs. nonresponders. Differential modulation of selected mRNAs was also observed between ustekinumab and etanercept PASI75 responders.
Project description:Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNFâµ/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. To define the transcriptomic profile of scalp skin, punch biopsies (6 mm diameter) were obtained from 20 Caucasian patients with untreated moderate to severe psoriasis with significative scalp involvement and 10 control subjects without psoriasis (N). Lesional (LS) samples were isolated from the infiltrated border of a plaque of psoriasis. Non lesional (NL) samples were taken from scalp areas with no visible psoriasis between the infiltrated plaques.
Project description:To understand the mechanism of disease progression in psoriasis, we defined Asian small plaque psoriasis (small psoriasis) and Asian intermediate plaque psoriasis (intermediate psoriasis) as psoriasis subtypes with limited disease progression, and compared their cellular and molecular signatures with the classic subtype of Western large plaque psoriasis (large psoriasis; GSE30999). Transcriptome analyses in pre-treatment skin biopsies from patients with Asian small and intermediate plaque psoriasis. 12 Asian small plaque psoriasis skin biopsy tissues (7 lesional and 5 non-lesional skin) and 15 Asian intermediate plaque psoriasis skin biopsy tissues (7 lesional and 8 non-lesional skin). GCRMA (using gcrma package from R/Bioconductor) and adjusted for batch effect. The expression data was combined with Western large psoriasis (GSE30999). Using a normalization based upon quantiles, the expression data was normalized based upon a specified normalization distribution of GSE30999 (see publication for GSE67853). The complete dataset representing: (1) 12 Asian small plaque psoriasis Samples, (2) 15 Asian intermediate plaque psoriasis Samples, and (3) 130 Western large plaque psoriasis Samples from GSE30999 (re-processed), is linked below as a supplementary file.
Project description:In the phase 3 VOYAGE-1 trial (ClinicalTrials.gov identifier: NCT02207231), guselkumab demonstrated superior efficacy versus placebo and the tumor necrosis factor (TNF)-α antagonist, adalimumab, in patients with moderate-to-severe plaque psoriasis (Blauvelt et al., 2017). Here, skin samples were collected from patients in VOYAGE-1 and pharmacodynamic (PD) responses to guselkumab (vs adalimumab) treatment were assessed over 48 weeks.