Abstract

Psoriasis is a common chronic inflammatory systemic disease. Epidermal proteins are considered to be important in maintaining skin barrier function, innate immunity, and inflammation. To define more possible roles of the epidermis in the pathogenesis of psoriasis, quantified proteomic analysis was used to screen and analyze the differentially expressed epidermal proteins between 16 psoriasis patients and 15 healthy controls. Upregulated differential expression proteins (DEPs) include several significant functional protein clusters, including antimicrobial peptides (AMPs) and antiviral proteins (AVPs). The levels of 2–5-oligoadenylate synthase 2 (OAS2) in both epidermis and serum levels were significantly elevated in psoriasis and were also positively correlated with Psoriasis Area Severity Index (PASI) scores and Body Surface Area (BSA) scores. Moreover, OAS2 expression in psoriatic skin significantly decreased after IL-17R mono-antibody treatment. It has been clarified that inflamed keratinocytes were the main source of abnormally increased OAS2 in psoriasis skin by immunofluorescence and primary cell cultures. Keratinocyte-derived OAS2 can be induced by not only IFNβ, but also psoriasis associated cytokines like IL-17A and IL-6. This study revealed that AMPs and AVPs are two important functional protein clusters altering innate immune in psoriatic epidermis. OAS2 is a novel potential sensitive biomarker, which could predict the severity and activity of psoriasis, and could also be used as an indicator to evaluate or monitor the efficacy of clinical treatment.

Highlights

  • Psoriasis vulgaris is a chronic immune-mediated inflammatory systemic disease, characterized by raised, well-demarcated, erythematous plaques with adherent silvery scales [1]

  • Skin biopsies were obtained from 16 patients suffering from psoriasis vulgaris

  • To test the integrity of the epidermis after dispase digestion, the separated epidermis was stained with Hematoxylin and Eosin (HE)

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Summary

Introduction

Psoriasis vulgaris is a chronic immune-mediated inflammatory systemic disease, characterized by raised, well-demarcated, erythematous plaques with adherent silvery scales [1]. High-throughput profiles including genome, epigenome, transcriptome, proteome, and metabolome have been performed in the last two decades [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. These omics-based discoveries have identified many promising biomarkers. There is a shift between differential expression genes (DEGs) and differential expression proteins (DEPs) in the same human psoriasis sample through transcriptome-proteome integration analysis [13]

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