Lipidomic Profiling of Peripheral Extracellular Vesicles as a Potential Source of Biomarkers in Gaucher Disease

Extracellular vesicles (EVs) are small, membrane-enclosed nanovesicles released by cells and play an essential role in cellular communication. EVs contain condensed information about physiological/pathological states, serving as fingerprints and providing access to candidate biomarkers with potential monitoring and prognostic value. In this context, we isolated EVs from serum and urine samples from patients with Gaucher disease type 1 (GD1), a lysosomal disease (LD) caused by glucocerebrosidase deficiency. Using LC-MS/MS lipidomics, we analyzed 52 serum- and urine-derived EVs from 15 patients with GD1, including those undergoing enzyme replacement therapy (ERT). EV specimens were biologically characterized and showed increased levels of glucosylceramide and related sphingolipids. Interestingly, in the lipidomic analysis, sphingomyelin, phosphoethanolamine (PE), plasmenyl-PE, phosphatidylcholine, and some triglyceride species showed a distinct pattern in GD1. The lipidomic profiles of isolated EVs change dynamically during ERT, supporting the potential utility of EV-based biomarkers for disease staging and assessment of therapeutic response. In sum, circulating EVs with specific lipidomic profiles reflecting pathophysiological conditions are a potential source of candidate GD1 biomarkers. Given that their biogenesis is closely linked to impairment of the endosomal/lysosomal system, as classically observed in GD1 and other LDs, EV-based lipid profiling may, after validation in independent cohorts, contribute to individualized and precise monitoring of current and emerging therapies for these disorders.