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Abstract：
Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus and skin nodules. Beyond the skin, PN involves circulating blood inflammation that may contribute to systemic disease comorbidities. Dupilumab was recently approved for treatment of PN, but its effects on systemic inflammation are unknown. Thus, we aimed to characterize changes in plasma concentrations of inflammatory proteins after dupilumab treatment. In this exploratory study, plasma samples were collected from 3 patients with moderate-to-severe PN before and after ≥6 months of dupilumab treatment. All patients exhibited clinically significant improvements after treatment. Of the 2569 proteins tested, 186 were differentially expressed after treatment (q < 0.1, fold change > 1.3). Downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Markers of innate immunity (IL-19, toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were also decreased (q < 0.1). Gene set variation analysis of Th2, Th17, and epithelial-mesenchymal transition gene sets showed reduced pathway expression in the post-treatment cohort (P < .05). Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFNG (R2 > 0.75, q < 0.10) showed the strongest correlations with pruritus severity. Dupilumab may reduce systemic inflammatory proteins associated with multiple immune and fibrosis pathways in patients with PN, potentially modulating the development of systemic disease comorbidities.
摘要：
结节性痒疹（PN）是一种慢性炎症性皮肤病，其特征是剧烈瘙痒和皮肤结节。超越皮肤，PN涉及循环血液炎症，可能导致全身性疾病合并症。Dupilumab最近被批准用于治疗PN，但其对全身炎症的影响尚不清楚。因此，我们旨在描述dupilumab治疗后血浆炎性蛋白浓度的变化.在这项探索性研究中，在dupilumab治疗≥6个月之前和之后,我们收集了3例中重度PN患者的血浆样本.所有患者在治疗后表现出临床上显著的改善。在测试的2569种蛋白质中，186个在处理后差异表达(q<0.1,倍数变化>1.3)。下调的蛋白包括与T辅助细胞（Th）1相关的细胞因子（IFN-γ，TNF-α)，Th2(IL-4,IL-13),和Th17/Th22(IL-6,IL-22)信号传导。先天免疫标志物（IL-19，Toll样受体1，一氧化氮合酶2），免疫细胞迁移（CCL20，CD177），纤维化（IL-11，IL-22）也降低（q<0.1）。Th2、Th17和上皮间质转化基因组的基因集变异分析显示治疗后队列中通路表达降低(P<0.05)。IL-11，一氧化氮合酶2，IL-13，IL-4和IFNG的血浆细胞因子水平（R2>0.75，q<0.10）显示出与瘙痒严重程度最强的相关性。Dupilumab可能减少与多种免疫和纤维化途径相关的全身炎症蛋白，可能调节全身性疾病合并症的发展。
