Ben-Fradj Mohamed Kacem, Naceur Ines, Talbi Emna, Wada Rahma, Feki Omar, Smiti-Khanfir Monia, Feki Moncef
Department of Biochemistry, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Department of Biochemistry & LR99ES11, Rabta Hospital, Tunis, Tunisia.
Korean J Intern Med. 2025 May;40(3):502-511. doi: 10.3904/kjim.2024.033. Epub 2025 Feb 21.
BACKGROUND/AIMS: Behçet's disease (BD) is an autoinflammatory disease of unknown etiopathogenesis. Oxylipins i.e., prostaglandins, leukotrienes, lipoxins, resolvins, and protectins are bioactive polyunsaturated fatty acids (PUFAs) derivatives involved in inflammatory response induction and resolution. The study aimed to determine the profile of selected PUFAs and oxylipins and to define a lipidomic signature for BD.
A case-control study was conducted involving thirty-five patients with BD and thirty-five age and sex-matched healthy individuals as a control group. Selected plasma PUFAs and oxylipins were analyzed using a targeted LC-MS/MS method.
The lipidomic profile was different between the two groups. BD patients showed higher levels of oxylipins deriving from either the n-6-arachidonic acid (i.e., prostaglandin D2, E2, F2α, and 6-keto-F1α, thromboxane B2, leukotriene B4, E4 and F4, and 6-epi and 15-epi-lipoxin A4) or n-3 PUFAs (i.e., 18-hydroxyeicosapentaenoic acid, 7,17-dihydroxy docosapentaenoic acid, protectin X, and resolvin D5), but decreased levels of both n-3 and n-6 PUFAs. Multivariate analyses selected the combination of four mediators, i.e., docosapentaenoic acid, prostaglandin E2, thromboxane B2, and lipoxin A4 as an accurate lipidomic signature for BD.
The profile of PUFAs/oxylipins is altered in BD patients, characterized by increased pro-inflammatory and pro-resolving oxylipins. The findings suggest that oxylipin metabolism might be involved in BD pathophysiology and may represent a therapeutic target for the disease. Further research is required to examine the role of lipid mediators in BD.
背景/目的:白塞病(BD)是一种病因发病机制不明的自身炎症性疾病。氧化脂质,即前列腺素、白三烯、脂氧素、消退素和保护素,是参与炎症反应诱导和消退的生物活性多不饱和脂肪酸(PUFA)衍生物。本研究旨在确定选定的PUFA和氧化脂质谱,并为BD定义一种脂质组学特征。
进行了一项病例对照研究,纳入35例BD患者和35例年龄及性别匹配的健康个体作为对照组。使用靶向液相色谱-串联质谱法分析选定的血浆PUFA和氧化脂质。
两组的脂质组学谱不同。BD患者中,源自n-6-花生四烯酸的氧化脂质(即前列腺素D2、E2、F2α和6-酮-F1α、血栓素B2、白三烯B4、E4和F4,以及6-表位和15-表位-脂氧素A4)或n-3多不饱和脂肪酸(即18-羟基二十碳五烯酸、7,17-二羟基二十二碳五烯酸、保护素X和消退素D5)水平较高,但n-3和n-6多不饱和脂肪酸水平均降低。多变量分析选择了四种介质的组合,即二十二碳五烯酸、前列腺素E2、血栓素B2和脂氧素A4,作为BD的准确脂质组学特征。
BD患者的PUFA/氧化脂质谱发生改变,其特征是促炎和促消退氧化脂质增加。这些发现表明氧化脂质代谢可能参与BD的病理生理过程,可能是该疾病的治疗靶点。需要进一步研究来探讨脂质介质在BD中的作用。