Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
11 2020
Historique:
received: 16 12 2019
accepted: 28 05 2020
entrez: 21 8 2020
pubmed: 21 8 2020
medline: 5 10 2021
Statut: epublish

Résumé

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. 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. 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. Immune profiling of plasmatic EVs represents a crucial step toward the identification of biomarkers of disease for PD and AP.

Identifiants

pubmed: 32817412
pii: 7/6/e866
doi: 10.1212/NXI.0000000000000866
pmc: PMC7428368
pii:
doi:

Substances chimiques

Antigens, Surface 0
Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Elena Vacchi (E)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Jacopo Burrello (J)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Dario Di Silvestre (D)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Alessio Burrello (A)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Sara Bolis (S)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Pierluigi Mauri (P)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Giuseppe Vassalli (G)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Carlo W Cereda (CW)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Cinthia Farina (C)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Lucio Barile (L)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Alain Kaelin-Lang (A)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Giorgia Melli (G)

From the Laboratory for Biomedical Neurosciences (E.V., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale; Faculty of Biomedical Sciences (E.V., G.V., L.B., A.K.-L., G.M.), Università della Svizzera Italiana; Cellular and Molecular Cardiology Laboratory (J.B., G.V.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Proteomic and Metabolomic Laboratory (D.D.S., P.M.), Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; Department of Electrical (A.B.), Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Italy; Laboratory for Cardiovascular Theranostics (S.B., L.B.), Cardiocentro Ticino Foundation, Lugano, Switzerland; Neurology Department (C.W.C., A.K.-L., G.M.), Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano; and Immunobiology of Neurological Disorders Lab (C.F.), Institute of Experimental Neurology (INSpe) and Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. giorgia.melli@eoc.ch.

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