Altered polyunsaturated fatty acids and oxylipins profile in Behçet’s disease

Abstract

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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.