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LB1144 Quantitative analysis of differentially expressed proteins in papulopustular rosacea

JOURNAL OF INVESTIGATIVE DERMATOLOGY(2019)

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Abstract
Papulopustular rosacea (PPR) is a chronic inflammatory skin disease which manifests as red, inflammatory papules or pustules predominantly on the facial region. Although the pathogenesis of PPR is not well understood, an over-reactive inflammatory response plays a role, resulting in altered vasculature and skin sensitivity. Although previous studies have assessed RNA expression or immunohistochemistry staining in tissue, to our knowledge this is the first-time quantitative protein analysis of PPR tissue has been performed. After IRB approval and informed consent, PPR patients (n=4) received biopsies of PPR and non-lesional skin. Biopsies were cultured for 24 hours and the conditioned culture medium subjected to two multiplex proteomic methods (OLINK® and MSD®) to quantify over 100 inflammatory proteins. We identified 21 proteins with statistically significant upregulation in PPR (p<0.05, adjusted for multiple hypothesis testing). There was significant upregulation of several IL-6 family cytokines, including IL-6, OSM, and LIF. Several chemokines also were significantly elevated in PPR, including CCL20, CCL8, CXCL5, and CCL3. Furthermore, we identified a complex adaptive inflammatory milieu in PPR, with statistically significant increases in both Th1 (IFNγ, IL-12p70, PD-L1, CXCL10) and Th2 associated proteins (CCL17, IL-4, IL-13, and IL-5). MMP-10, FGF-19, and LAP-TGF-beta were also significantly increased, potentially indicating tissue remodeling. Other significantly increased proteins were OPG, AXIN1, and uPA. In this first quantitative protein analysis, we identified new inflammatory proteins not previously described in PPR. These findings may help to identify novel and relevant pathways to target to better treat PPR.
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proteins
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