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      Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay

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          Abstract

          Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void in objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested to determine concentrations of IL-19 serum levels, then correlated with the psoriasis activity and severity index (PASI) in psoriasis, and the eczema area and severity index (EASI) in atopic dermatitis. Not only was IL-19 increased in psoriasis and correlated to PASI, but ixekizumab administration led to rapid, sustained IL-19 decreases to normal levels, with decreases at 2-weeks correlating with PASI improvement at 16-weeks. IL-19 increased upon ixekizumab withdraw, prior to relapse, and decreased following re-treatment. In baricitinib- and etanercept-treated psoriasis patients, IL-19 decreases also correlated with improvement. Many patients with limited skin disease, including genital psoriasis and psoriatic arthritis patients, also had increased IL-19, which was reduced to normal levels upon ixekizumab treatment, correlating with PASI improvement. We also measured IL-19 in baricitinib-treated atopic dermatitis patients. In atopic dermatitis, IL-19 was significantly elevated, correlated with EASI scores, and decreased with skin improvement. Therefore, measurement of serum IL-19 provides clinicians with an objective disease-activity assessment tool for psoriasis and atopic dermatitis patients.

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          Most cited references42

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          Severe Psoriasis – Oral Therapy with a New Retinoid

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            Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis.

            Psoriasis is a complex inflammatory disease mediated by tumor necrosis factor (TNF)-α and cytokines secreted by specialized T-cell populations, e.g., IL-17, IL-22, and IFN-γ. The mechanisms by which innate and adaptive immune cytokines regulate inflammation in psoriasis are not completely understood. We sought to investigate the effects of TNF-α and IL-17 on keratinocyte (KC) gene profile, to identify genes that might be coregulated by these cytokines and determine how synergistically activated genes relate to the psoriasis transcriptome. Primary KCs were stimulated with IL-17 or TNF-α alone, or in combination. KC responses were assessed by gene array analysis, followed by reverse transcriptase-PCR confirmation for significant genes. We identified 160 genes that were synergistically upregulated by IL-17 and TNF-α, and 196 genes in which the two cytokines had at least an additive effect. Synergistically upregulated genes included some of the highest expressed genes in psoriatic skin with an impressive correlation between IL-17/TNF-α-induced genes and the psoriasis gene signature. KCs may be key drivers of pathogenic inflammation in psoriasis through integrating responses to TNF-α and IL-17. Our data predict that psoriasis therapy with either TNF or IL-17 antagonists will produce greater modulation of the synergistic/additive gene set, which consists of the most highly expressed genes in psoriasis skin lesions.
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              The IL-20 subfamily of cytokines--from host defence to tissue homeostasis.

              The interleukin-20 (IL-20) subfamily of cytokines comprises IL-19, IL-20, IL-22, IL-24 and IL-26. These cytokines are all members of the larger IL-10 family, but have been grouped together to form the IL-20 subfamily based on their usage of common receptor subunits and similarities in their target-cell profiles and biological functions. Members of the IL-20 subfamily facilitate the communication between leukocytes and epithelial cells, thereby enhancing innate defence mechanisms and tissue repair processes at epithelial surfaces. In this Review, we describe the cellular sources and targets of the IL-20 subfamily cytokines, and we detail how their expression is regulated. Much of our understanding of the unique biology of this group of cytokines is still based on IL-22, which is the most studied member of the IL-20 subfamily. Nevertheless, we attempt a broader discussion of the emerging functions of IL-20 subfamily cytokines in host defence, inflammatory diseases, cancer and metabolism.
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                Author and article information

                Contributors
                b.nickoloff@lilly.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                26 March 2019
                26 March 2019
                2019
                : 9
                : 5211
                Affiliations
                ISNI 0000 0000 2220 2544, GRID grid.417540.3, Lilly Research Laboratories, Eli Lilly and Company, ; Indianapolis, IN 46285 USA
                Article
                41609
                10.1038/s41598-019-41609-z
                6435799
                30914699
                6fdbb3ab-9d9a-4d05-9309-27b8b6c667e6
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 December 2018
                : 12 March 2019
                Funding
                Funded by: Eli Lilly and Company
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