Potential Role of CHI3L1+ Astrocytes in Progression in MS.
Adult
Aged
Aged, 80 and over
Astrocytes
Biomarkers
/ cerebrospinal fluid
Chitinase-3-Like Protein 1
/ blood
Cohort Studies
Cross-Sectional Studies
Demyelinating Diseases
/ cerebrospinal fluid
Disease Progression
Female
Humans
Inflammation
/ metabolism
Male
Middle Aged
Multiple Sclerosis, Chronic Progressive
/ cerebrospinal fluid
Neurofilament Proteins
/ cerebrospinal fluid
Retrospective Studies
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:
04 05 2021
04 05 2021
Historique:
received:
29
06
2020
accepted:
21
12
2020
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
3
11
2021
Statut:
epublish
Résumé
Neurofilament light protein (NfL) and chitinase 3-like 1 (CHI3L1) are biomarkers for acute neuroaxonal damage and local inflammation, respectively. Thus, we set out to evaluate how these biomarkers were associated with clinical features of demyelinating diseases in parallel with the expression in brain autopsies from patients with similar disease stages, assuming their comparability. NfL and CHI3L1 in CSF and serum CHI3L1 were assessed retrospectively in a cross-sectional cohort of controls (n = 17) and patients diagnosed with MS (n = 224), relapsing (n = 163) or progressive (n = 61); neuromyelitis optica (NMO, n = 7); and acute disseminated encephalomyelitis (ADEM, n = 15). Inflammatory activity was evaluated at the time of sampling, and CSF biomarker levels were related to the degree of inflammation in 22 brain autopsy tissues. During a clinical attack, the CSF NfL increased in MS, NMO, and ADEM, whereas CHI3L1 was only elevated in patients with NMO and ADEM and in outlier MS patients with extensive radiologic activity. Outside relapses, CHI3L1 levels only remained elevated in patients with progressive MS. CHI3L1 was detected in macrophages and astrocytes, predominantly in areas of active demyelination, and its expression by astrocytes in chronic lesions was independent of lymphocyte infiltrates and associated with active neurodegeneration. Both CSF NfL and CHI3L1 augment during acute inflammation in demyelinating diseases. In MS, CHI3L1 may be associated with low-grade nonlymphocytic inflammation and active neurodegeneration and therefore linked to progressive disease. This study provides Class III evidence that CSF NfL and CHI3L1 levels increase in inflammatory brain diseases during acute inflammation.
Identifiants
pubmed: 33658322
pii: 8/3/e972
doi: 10.1212/NXI.0000000000000972
pmc: PMC7931642
pii:
doi:
Substances chimiques
Biomarkers
0
Chitinase-3-Like Protein 1
0
Neurofilament Proteins
0
neurofilament protein L
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Front Neurol. 2019 Sep 23;10:1008
pubmed: 31608004
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
Mult Scler. 2017 Nov;23(13):1727-1735
pubmed: 28831853
Biol Psychiatry. 2010 Nov 15;68(10):903-12
pubmed: 21035623
Brain. 2015 Apr;138(Pt 4):918-31
pubmed: 25688078
J Neuroimmunol. 2016 Oct 15;299:112-117
pubmed: 27725108
Neurology. 2014 Jul 15;83(3):278-86
pubmed: 24871874
J Neuropathol Exp Neurol. 2012 Nov;71(11):948-58
pubmed: 23041842
Annu Rev Physiol. 2011;73:479-501
pubmed: 21054166
Ann Neurol. 2000 Jun;47(6):707-17
pubmed: 10852536
Ann Neurol. 1995 Nov;38(5):788-96
pubmed: 7486871
Aging (Albany NY). 2018 Sep 13;10(9):2367-2382
pubmed: 30215603
J Neurol Sci. 2003 Feb 15;206(2):165-71
pubmed: 12559505
Neurology. 2009 Dec 1;73(22):1914-22
pubmed: 19949037
Mult Scler. 2012 Jul;18(7):983-90
pubmed: 22183936
Lancet Neurol. 2018 Feb;17(2):162-173
pubmed: 29275977
Front Neurol. 2019 Mar 26;10:280
pubmed: 30972011
J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):137-145
pubmed: 27671902
Neurology. 2015 Jul 14;85(2):177-89
pubmed: 26092914
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
Exp Neurol. 2020 Jan;323:113082
pubmed: 31669069
Mol Neurodegener. 2017 Nov 10;12(1):83
pubmed: 29126445
Neurol Neuroimmunol Neuroinflamm. 2019 Jul 19;6(5):
pubmed: 31454774
Neuropathol Appl Neurobiol. 2011 Dec;37(7):698-710
pubmed: 21696413
Clin Immunol. 2015 Dec;161(2):354
pubmed: 26477483
Sci Rep. 2020 Apr 28;10(1):7118
pubmed: 32346016
Brain. 2017 Jul 1;140(7):1900-1913
pubmed: 28541408
Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):
pubmed: 29358320
J Neurol Sci. 1984 Mar;63(3):423-33
pubmed: 6202848
Neurology. 2017 Feb 28;88(9):826-831
pubmed: 28148632
Mult Scler Relat Disord. 2018 Aug;24:175-183
pubmed: 30055504
J Neuroinflammation. 2010 Jun 11;7:34
pubmed: 20540736
Mult Scler. 2013 Sep;19(10):1261-7
pubmed: 23572237
Mult Scler. 2014 Jul;20(8):1086-94
pubmed: 24323817
Expert Rev Proteomics. 2017 Apr;14(4):285-299
pubmed: 28281838
J Biol Chem. 2003 Nov 7;278(45):44058-67
pubmed: 12933821
J Neuroimmunol. 2016 Mar 15;292:52-7
pubmed: 26943959
Brain Pathol. 2012 Jul;22(4):530-46
pubmed: 22074331
Mult Scler. 2011 May;17(5):521-31
pubmed: 21159721
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
Curr Neuropharmacol. 2017;15(6):906-917
pubmed: 28183245
Ann Neurol. 2015 Nov;78(5):710-21
pubmed: 26239536
Acta Neuropathol. 2013 Jun;125(6):815-27
pubmed: 23579868
Tohoku J Exp Med. 2008 May;215(1):55-9
pubmed: 18509235