Extracellular vesicle proteomics identifies novel blood biomarkers for the early diagnosis of status epilepticus

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OBJECTIVE: This study was undertaken to identify novel blood-based biomarkers associated with the early diagnosis of status epilepticus (SE) by exploring proteomic alterations in plasma extracellular vesicles (EVs). METHODS: We conducted an observational and prospective study in a two-phase design: a discovery proteomic analysis of plasma EVs from 16 patients (eight with SE and eight matched non-SE), followed by a validation phase using basic immunodetection techniques in a separate cohort of 160 patients (80 SE, 80 non-SE) for selected proteins in plasma. Proteomic profiling was performed with liquid chromatography-tandem mass spectrometry, and protein interaction networks were explored using STRING and Cytoscape software platforms. RESULTS: In the discovery phase, 2046 proteins were identified, and 977 met inclusion criteria. CDH1, APOC4, and IGHG2 showed the highest differential expression in SE patients. Network analysis revealed strong interactions involving SLC4A1 and SRC. In the validation cohort, levels of APOC4, CDH1, SLC4A1, and S100B were significantly higher in SE patients (p < .05). In the multivariate logistic regression model, only APOC4, S100B, and SLC4A1 remained independently associated with SE diagnosis. A combined model including these proteins predicted SE with 84.6% accuracy (95% confidence interval = 64.3%-94.9%). Other proteins, including NSE and HMGB1, showed no significant differences. SIGNIFICANCE: This study identifies new plasma biomarkers that may support the early diagnosis of SE, particularly in emergency settings where access to electroencephalography is limited. These findings suggest potential applicability to clinical practice; nevertheless, prospective validation in independent and larger cohorts is required.

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