Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease.
Aged
Aged, 80 and over
Antigens, Surface
Biomarkers
/ blood
Case-Control Studies
Cross-Sectional Studies
Extracellular Vesicles
/ immunology
Female
Flow Cytometry
Humans
Male
Middle Aged
Multiple System Atrophy
/ blood
Parkinson Disease
/ blood
Parkinsonian Disorders
/ blood
Protein Interaction Maps
Sensitivity and Specificity
Supervised Machine Learning
Tauopathies
/ blood
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
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.
Références
Int J Mol Sci. 2016 Feb 02;17(2):
pubmed: 26848654
Neurology. 2008 Aug 26;71(9):670-6
pubmed: 18725592
Neurology. 2003 Sep 9;61(5):686-9
pubmed: 12963764
Front Immunol. 2016 Jul 26;7:282
pubmed: 27507971
J Extracell Vesicles. 2016 Feb 19;5:29975
pubmed: 26901056
Immunol Rev. 2009 May;229(1):152-72
pubmed: 19426221
Mov Disord. 2006 Jan;21(1):89-93
pubmed: 16108021
J Allergy Clin Immunol. 2019 Sep;144(3):825-838
pubmed: 30926529
Mov Disord. 2012 Sep 15;27(11):1364-9
pubmed: 22927213
N Engl J Med. 2018 Sep 06;379(10):958-966
pubmed: 30184457
Neurobiol Dis. 2006 Feb;21(2):404-12
pubmed: 16182554
Ann Surg. 2019 Jan 18;:
pubmed: 30672800
Mov Disord. 2017 Jun;32(6):853-864
pubmed: 28467028
Eur J Neurosci. 2019 Feb;49(3):364-383
pubmed: 30474172
Front Pharmacol. 2012 Feb 17;3:15
pubmed: 22363285
Nat Rev Immunol. 2002 Aug;2(8):569-79
pubmed: 12154376
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1926-35
pubmed: 25825709
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Brain Behav Immun. 2017 Feb;60:188-197
pubmed: 27751869
J Parkinsons Dis. 2018;8(3):385-398
pubmed: 29991141
Sci Rep. 2018 Sep 5;8(1):13276
pubmed: 30185816
Arch Neurol. 2011 Aug;68(8):1037-9
pubmed: 21825240
Neuroendocrinology. 2018;107(2):181-195
pubmed: 29439247
Cell Death Discov. 2017 Mar 06;3:17005
pubmed: 28280601
Neurology. 2013 Jan 29;80(5):496-503
pubmed: 23359374
Mol Med Rep. 2018 Mar;17(3):3775-3782
pubmed: 29257331
Parkinsonism Relat Disord. 2019 Apr;61:82-87
pubmed: 30502924
Lancet Neurol. 2006 Jan;5(1):75-86
pubmed: 16361025
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt A):1190-1199
pubmed: 28286014
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Neurology. 2015 Jul 7;85(1):40-7
pubmed: 26062630
Neuron. 2018 Dec 19;100(6):1337-1353.e5
pubmed: 30415998
Mol Cell Neurosci. 2006 Apr;31(4):642-8
pubmed: 16446100
Nature. 2017 Jun 29;546(7660):656-661
pubmed: 28636593
J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
pubmed: 1564476
Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7622-E7631
pubmed: 28827364
J Neurol Neurosurg Psychiatry. 2020 Jul;91(7):720-729
pubmed: 32273329
Brain Behav Immun. 2018 Mar;69:591-602
pubmed: 29458199
Mov Disord. 2004 Oct;19(10):1221-6
pubmed: 15390000
Ann Clin Transl Neurol. 2015 Apr;2(4):353-61
pubmed: 25909081
Front Aging Neurosci. 2019 Jan 14;10:438
pubmed: 30692923
F1000Res. 2014 Jul 01;3:139
pubmed: 26594322
Nanomedicine. 2011 Dec;7(6):780-8
pubmed: 21601655
J Parkinsons Dis. 2017;7(4):569-576
pubmed: 28922170
J Autoimmun. 2012 May;38(2-3):J144-55
pubmed: 22119415
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
J Steroid Biochem Mol Biol. 2019 May;189:274-282
pubmed: 30654107
EURASIP J Bioinform Syst Biol. 2017 Dec;2017(1):6
pubmed: 28477207
F1000Res. 2015 Aug 5;4:484
pubmed: 27781081