Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear. Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment. The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.

中文翻译：

---

代谢分析显示，IL-17A 单克隆抗体治疗可改善脂质代谢，并有可能降低银屑病患者的心血管风险

银屑病是一种常见的慢性炎症性皮肤病，与白细胞介素 17A (IL-17A) 的过度产生有关。IL-17A 单克隆抗体 (mAb) 已在银屑病患者中显示出临床疗效。尽管已发现一系列不同的重叠机制在银屑病和心血管疾病之间建立联系，但这两种疾病的潜在机制以及 IL-17A mAb 在改善心血管合并症方面的潜在功效仍不清楚。使用高通量 UHPLC-MS 平台分析了来自两个研究队列（包括 117 个人）的血清样本。在研究队列 1 中，首先对 28 名健康个体和 28 名银屑病患者在 ixekizumab 治疗 12 周之前和之后的样本进行了非靶向代谢谱分析。另外招募了研究队列 2 以验证已鉴定代谢物与心血管疾病的相关性。在研究队列 1 中，共准确鉴定了 43 种差异代谢物，包括溶血磷脂、游离脂肪酸、酰基肉碱和二羧酸，分析表明银屑病患者的脂质代谢受损。与健康人相比，银屑病患者的溶血磷脂酰胆碱、溶血磷脂酰肌醇、溶血磷脂酸和游离脂肪酸水平较高，但酰基肉碱和二羧酸水平较低。确定的二羧酸水平与银屑病面积和严重程度指数 (PASI) 评分呈负相关 (P < 0.05)。研究队列 2 的结果与研究队列 1 的结果基本一致。此外，所有鉴定出的溶血磷脂酰胆碱水平在患有冠心病的银屑病患者中高于没有冠心病的银屑病患者。值得注意的是，ixekizumab 治疗可以改善大多数这些脂质变化。这种非靶向代谢组学分析的结果表明，用 IL-17A mAb 治疗不仅可以改善银屑病病变，还可以将银屑病患者失调的脂质代谢恢复到正常水平。考虑到脂质代谢失调被认为是心血管疾病的关键因素，银屑病患者脂质代谢物的恢复表明 IL-17A mAb 可能对心血管合并症具有潜在的保护作用。