IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions

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IL-36γ (IL-1F9) Is a Biomarker for Psoriasis Skin Lesions Angelo Massimiliano D'Erme, Dagmar Wilsmann-Theis, Julia Wagenpfeil, Michael Hölzel, Sandra Ferring-Schmitt, Sonja Sternberg, Miriam Wittmann, Bettina Peters, Andreas Bosio, Thomas Bieber, Joerg Wenzel Journal of Investigative Dermatology Volume 135, Issue 4, Pages 1025-1032 (April 2015) DOI: 10.1038/jid.2014.532 Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Gene expression analyses of lesional skin (psoriasis and other inflammatory skin diseases). (a) Unsupervised hierarchical gene cluster analysis including all 189 specifically expressed genes in one of the diseases as identified by Significance Analysis for Microarrays (SAM) (>2-fold expressed, P<0.01). (b) Top 10 upregulated genes in psoriasis when compared with HC, CE, LP, and AD, identified via SAM. (c) Volcano plot including all 1,539 genes of the original data set. Higher y-axis values (-log10 transformed P-values) correspond to a higher significance level of differentially expressed genes in a two-group comparison (psoriasis versus other skin diseases). The x-axis indicates the difference in gene expression between the two groups. Gene expression values were log2 transformed to ensure normal distribution. Positive values indicate higher expression in psoriasis samples versus other skin diseases and vice versa for negative values. AD, atopic dermatitis; CE, contact eczema; HC, healthy controls; LP, lichen planus; Pso, psoriasis vulgaris. n=150. Journal of Investigative Dermatology 2015 135, 1025-1032DOI: (10.1038/jid.2014.532) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 IL-36γ gene and protein expression in psoriasis and other skin diseases. (a) Individual gene expression score of IL-36γ in psoriasis skin lesions and controls (n=30 for each subset). Comparison of IL-36γ gene expression in psoriasis versus HC, AD, LP, and CE: each comparison significant with P<0.01 (Mann–Whitney U-test). (b) Protein expression of IL-36γ in different erythrosquamous skin diseases (mean expression±SEM; P<0.01, Mann–Whitney U-test) and corresponding representative immunohistological micrographs (original magnification × 200, scale bar=0.1 mm). n=10 for HC, AD, LP, Pso, and CE, respectively, and n=5 for PL, SCLE, Tinea, and MF, respectively. (c) Correlation (Spearman’s ρ) between gene expression and histological score. Included are 40 of the original samples, with n=10 for HC, AD, LP, and Pso, respectively. HC, healthy controls; AD, atopic dermatitis; LP, lichen planus; Pso, psoriasis vulgaris; CE, contact eczema; PL, pityriasis lichenoides; SCLE, subacute cutaneous lupus erythematosus; MF, mycosis fungoides. Journal of Investigative Dermatology 2015 135, 1025-1032DOI: (10.1038/jid.2014.532) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 IL-36γ peripheral blood serum levels and predictive value of IL-36γ immunohistochemistry. (a) Mean IL-36γ blood serum levels±SEM in untreated patients with psoriasis (Pso, n=7), atopic dermatitis (AD, n=5), and healthy controls (HCs, n=7). (b) Correlation (Spearman’s ρ) between PASI (psoriasis area and severity index) score and IL-36γ serum levels in treated and untreated individuals (Psountreated n=7, Psotreated n=7, and HCs, n=7). (c) Individual and mean IL-36γ serum levels in untreated (baseline) and etanercept-treated (after 24 weeks of treatment) psoriasis patients. Wilcoxon signed-rank test. (d) Representative micrographs of psoriasis and eczema skin biopsies (hematoxylin and eosin staining, IL-36γ immunohistochemistry, original magnification × 200, scale bar=0.1 mm); table of predictive value of IL-36γ immunohistochemistry (divided into three categories depending on the amount of cell layers stained: ⩾4/2–3/⩽1 cell layers; n=21). Pso, psoriasis vulgaris. Journal of Investigative Dermatology 2015 135, 1025-1032DOI: (10.1038/jid.2014.532) Copyright © 2015 The Society for Investigative Dermatology, Inc Terms and Conditions