3 years ago

The genetics of chronic itch: gene expression in the skin of atopic dermatitis and psoriasis patients with severe itch.

Christian Albornoz, Gil Yosipovitch, Kristen M Sanders, Rodrigo Valdes-Rodriguez, Leigh A Nattkemper, Helen Lee, Hong Liang Tey, Nicholas K Mollanazar
To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and non-itchy, non-lesional skin biopsies from 25 atopic dermatitis (AD) and 25 psoriasis patients and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared to healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and non-itchy skin in atopic and psoriatic subjects. Overexpression of several genes, such as phospholipase A2 IVD, substance P, Nav1.7, and TRPV1, in itchy skin was positively correlated to itch intensity ratings in both AD and psoriasis. Cytokines such as IL-17A, IL-23A, and IL-31 had elevated gene transcript levels in both itchy atopic and psoriatic skin. However, expression of genes for TRPV2, TRPA1, PAR2, PAR 4, and IL-10 was found to be increased only in pruritic atopic skin, while expression of genes for TRPM8, TRPV3, phospholipase C, and IL-36α/γ was elevated only in pruritic psoriatic skin. This "itchscriptome" analysis will lead to an increased understanding of the molecular mechanisms of chronic pruritus and provide targets for itch treatment irrespective of disease state.

Publisher URL: http://doi.org/10.1016/j.jid.2017.12.029

DOI: 10.1016/j.jid.2017.12.029

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