Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease. Issue 6 (November 2020)

• Record Type: Journal Article
• Authors: Vacchi, Elena; Burrello, Jacopo; Di Silvestre, Dario; Burrello, Alessio; Bolis, Sara; Mauri, Pierluigi; Vassalli, Giuseppe; Cereda, Carlo W.; Farina, Cinthia; Barile, Lucio; Kaelin-Lang, Alain; Melli, Giorgia
• Is Part Of: Neurology. Volume 7:Issue 6(2020)
• Publication Date: 2020-11
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000866
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Objective: 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. Methods: 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. Results: 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. Conclusions: Immune profiling of plasmatic EVs represents a crucial step toward the identification of biomarkers of disease for PD and AP.