Plasma Lipidomic Remodeling in Behçet's Disease Reveals Alterations Associated with Vascular Involvement

Background/Objectives: Behçet's disease (BD) is a chronic multisystem inflammatory disorder in which vascular involvement represents a major cause of morbidity and mortality. However, the molecular mechanisms underlying vascular involvement remain poorly understood. Lipidomics offers a powerful approach to investigate disease-associated metabolic alterations at the lipid level. Methods: Plasma lipidomic profiles were analyzed in 48 patients with BD, including 18 with vascular involvement, and 40 age- and sex-matched healthy controls. Lipids were extracted using a chloroform-methanol-based protocol and analyzed by LC-qTOF-MS. Data processing and lipid annotation were performed using MS-DIAL. Multivariate and univariate statistical analyses, together with class-based KEGG pathway mapping, were applied to evaluate lipidomic alterations. Results: Principal component analysis demonstrated a clear separation between BD patients and healthy controls, indicating extensive lipidomic remodeling. BD was associated with significant alterations in phosphatidylcholines, sphingomyelins, diacylglycerols, and triacylglycerols, reflecting coordinated changes in membrane structure, lipid-mediated signaling, and energy metabolism. Pathway analysis further supported the involvement of glycerophospholipid, glycerolipid, and phosphatidylinositol-related metabolic pathways. Comparison between BD patients with and without vascular involvement revealed no major global lipidomic shift; however, specific lipid species showed consistent alterations. Two phosphatidylcholine species (PC 33:2 and ether-linked PC 31:4e) were decreased, whereas one triacylglycerol species (TAG 58:2) was increased in patients with vascular involvement. Conclusions: These findings suggest that BD is characterized by coordinated lipidomic reprogramming involving membrane remodeling, inflammatory signaling, and metabolic adaptation. Vascular involvement appears to be associated with subtle, lipid-specific alterations rather than a global lipidomic shift, highlighting potential molecular features of disease progression.