Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease
<h3>Objective</h3> To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform. <h3>Methods</h3> Plasma-derived...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Format: | Artigo |
| Sprache: | Englisch |
| Veröffentlicht: |
2020
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| Online-Zugang: | https://doi.org/10.1212/nxi.0000000000000866 https://nn.neurology.org/content/nnn/7/6/e866.full.pdf |
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| Zusammenfassung: | <h3>Objective</h3> To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform. <h3>Methods</h3> Plasma-derived EVs were isolated from PD, matched healthy controls, multiple system atrophy (MSA), and AP with tauopathies (AP-Tau). The expression levels of 37 EV surface markers were measured by flow cytometry and correlated with clinical scales. A diagnostic model based on EV surface markers expression was built via supervised machine learning algorithms and validated in an external cohort. <h3>Results</h3> Distinctive pools of EV surface markers related to inflammatory and immune cells stratified patients according to the clinical diagnosis. PD and MSA displayed a greater pool of overexpressed immune markers, suggesting a different immune dysregulation in PD and MSA vs AP-Tau. The receiver operating characteristic curve analysis of a compound EV marker showed optimal diagnostic performance for PD (area under the curve [AUC] 0.908; sensitivity 96.3%, specificity 78.9%) and MSA (AUC 0.974; sensitivity 100%, specificity 94.7%) and good accuracy for AP-Tau (AUC 0.718; sensitivity 77.8%, specificity 89.5%). A diagnostic model based on EV marker expression correctly classified 88.9% of patients with reliable diagnostic performance after internal and external validations. <h3>Conclusions</h3> Immune profiling of plasmatic EVs represents a crucial step toward the identification of biomarkers of disease for PD and AP. |
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