杜匹单抗相关眼表疾病的特应性皮炎患者的代谢组学和脂质组学改变

VijayKumar Patra , Nora Woltsche , Natalie Bordag , Urban Cerpes , Danijela Bokanovic , Maria Repelnig , Yohann Clement , Isabella Perchthaler , Harald Köfeler , Manuela Fischl , Franz Legat , Andreas Wedrich , Jutta Horwath-Winter , Sophie Ayciriex , Peter Wolf
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引用次数: 0

摘要

特应性皮炎(AD)是一种以慢性瘙痒性湿疹为特征的炎症性皮肤病,估计成人患病率为10%,其中50%患有中度至重度症状。Dupilumab是一种IL-4/IL-13抑制剂,被批准用于治疗中重度AD。然而,高达60%的dupilumab治疗患者出现dupilumab相关的眼表疾病(DAOSD),构成主要的ad特异性不良事件。DAOSD的发病机制尚不完全清楚。为了阐明dupilumab治疗AD患者后发生的代谢变化,我们将这项前瞻性单中心队列研究重点放在了DAOSD患者身上。共有20例AD患者接受了dupilumab治疗,其中6例发生DAOSD。在基线、治疗开始后4周和16周以及结膜炎发作期间收集血浆和血清样本。此外,10名年龄和性别匹配的健康对照在基线时单独取样。采用高分辨率质谱法对所有血液样本进行代谢组学和脂质组学分析。靶向代谢组学和脂质组学与多变量分析揭示了AD患者与非DAOSD患者之间显著的代谢和脂质差异(如苯甲酸、酪氨酸和吲哚代谢活性增加等)。代谢组学和脂质组学分析进一步加深了我们对DAOSD发病机制的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Metabolomic and Lipidomic Alterations in Patients with Atopic Dermatitis with Dupilumab-Associated Ocular Surface Disease

Metabolomic and Lipidomic Alterations in Patients with Atopic Dermatitis with Dupilumab-Associated Ocular Surface Disease
Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic pruritic eczema with an estimated prevalence of 10% in adults and 50% of them suffering from moderate-to-severe manifestations. Dupilumab, an IL-4/IL-13 inhibitor, is approved for treating moderate-to-severe AD. However, dupilumab-associated ocular surface disease (DAOSD) emerges in up to 60% of dupilumab-treated patients, constituting a major AD-specific adverse event. DAOSD pathogenesis has not been fully understood yet. To elucidate the metabolic changes occurring after dupilumab treatment in patients with AD, we focused in this prospective single-center cohort study particularly on patients who developed DAOSD. In total, 20 patients with AD underwent dupilumab therapy, with 6 developing DAOSD. Plasma and serum samples were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. In addition, 10 age- and sex-matched healthy controls were sampled solely at baseline. High-resolution mass spectrometry was employed for metabolomic and lipidomic analysis of all blood samples. Targeted metabolomics and lipidomic with multivariate analysis unveiled significant metabolic and lipidic disparities (such as increased activity of benzoic acid, tyrosine and indole metabolism, and others) between AD patients with and those without DAOSD. Metabolomics and lipidomic analysis further deepen our comprehension of DAOSD pathogenesis.
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