Serum Glial Fibrillary Acidic Protein: A Neuromyelitis Optica Spectrum Disorder Biomarker.
Adolescent
Adult
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Biomarkers
/ blood
Double-Blind Method
Female
Glial Fibrillary Acidic Protein
/ blood
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
/ blood
Neuromyelitis Optica
/ blood
Prospective Studies
Risk Assessment
Survival Analysis
Treatment Outcome
Young Adult
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
09
03
2021
received:
21
10
2020
accepted:
10
03
2021
pubmed:
17
3
2021
medline:
27
5
2021
entrez:
16
3
2021
Statut:
ppublish
Résumé
Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment. N-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial in adults with NMOSD. sGFAP levels were measured by single-molecule arrays (SIMOA) in 1,260 serial and attack-related samples from 215 N-MOmentum participants (92% aquaporin 4-immunoglobulin G-seropositive) and in control samples (from healthy donors and patients with relapsing-remitting multiple sclerosis). At baseline, 62 participants (29%) exhibited high sGFAP concentrations (≥170 pg/ml; ≥2 standard deviations above healthy donor mean concentration) and were more likely to experience an adjudicated attack than participants with lower baseline concentrations (hazard ratio [95% confidence interval], 3.09 [1.6-6.1], p = 0.001). Median (interquartile range [IQR]) concentrations increased within 1 week of an attack (baseline: 168.4, IQR = 128.9-449.7 pg/ml; attack: 2,160.1, IQR = 302.7-9,455.0 pg/ml, p = 0.0015) and correlated with attack severity (median fold change from baseline [FC], minor attacks: 1.06, IQR = 0.9-7.4; major attacks: 34.32, IQR = 8.7-107.5, p = 0.023). This attack-related increase in sGFAP occurred primarily in placebo-treated participants (FC: 20.2, IQR = 4.4-98.3, p = 0.001) and was not observed in inebilizumab-treated participants (FC: 1.1, IQR = 0.8-24.6, p > 0.05). Five participants (28%) with elevated baseline sGFAP reported neurological symptoms leading to nonadjudicated attack assessments. Serum GFAP may serve as a biomarker of NMOSD activity, attack risk, and treatment effects. ANN NEUROL 2021;89:895-910.
Identifiants
pubmed: 33724534
doi: 10.1002/ana.26067
pmc: PMC8252046
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
GFAP protein, human
0
Glial Fibrillary Acidic Protein
0
inebilizumab
74T7185BMM
Banques de données
ClinicalTrials.gov
['NCT02200770']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-910Subventions
Organisme : NEI NIH HHS
ID : R01 EY022936
Pays : United States
Investigateurs
Kazuo Fujihara
(K)
Friedemann Paul
(F)
Hans-Peter Hartung
(HP)
Romain Marignier
(R)
Ho Jin Kim
(HJ)
Brian G Weinshenker
(BG)
Sean J Pittock
(SJ)
Dean M Wingerchuk
(DM)
Gary R Cutter
(GR)
Ari J Green
(AJ)
Maureen A Mealy
(MA)
Jorn Drappa
(J)
Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Neurology. 2019 Sep 24;93(13):e1299-e1311
pubmed: 31471502
J Neurol. 2016 Jul;263(7):1343-8
pubmed: 27142716
Mult Scler. 2014 Apr;20(5):617-20
pubmed: 24009163
Clin Chim Acta. 2013 Jun 5;421:181-3
pubmed: 23535508
JAMA Neurol. 2016 Nov 1;73(11):1342-1348
pubmed: 27668357
J Clin Med. 2016 Nov 24;5(12):
pubmed: 27886126
Neurol Neuroimmunol Neuroinflamm. 2015 May 21;2(4):e110
pubmed: 26185772
Curr Opin Neurol. 2019 Jun;32(3):385-394
pubmed: 30893099
Neurology. 2005 Apr 12;64(7):1270-2
pubmed: 15824362
Eur J Neurol. 2017 Apr;24(4):652-658
pubmed: 28233435
Acta Neuropathol. 2010 Jan;119(1):7-35
pubmed: 20012068
Mult Scler. 2019 Feb;25(2):235-245
pubmed: 29143550
N Engl J Med. 2019 Aug 15;381(7):614-625
pubmed: 31050279
Arthritis Res Ther. 2016 Jun 07;18(1):131
pubmed: 27267753
Neurology. 1999 Sep 22;53(5):1107-14
pubmed: 10496275
J Neurol Neurosurg Psychiatry. 2009 May;80(5):575-7
pubmed: 19372295
Ann Neurol. 2009 Nov;66(5):617-29
pubmed: 19938104
Mult Scler. 2020 Feb;26(2):210-219
pubmed: 30570436
Neurol Neuroimmunol Neuroinflamm. 2016 Apr 14;3(3):e224
pubmed: 27144215
Brain Pathol. 2014 Jan;24(1):83-97
pubmed: 24345222
Mult Scler. 2016 Jun;22(7):862-72
pubmed: 26666258
Lancet Neurol. 2013 Jun;12(6):554-62
pubmed: 23623397
J Clin Invest. 2009 Jul;119(7):1814-24
pubmed: 19587456
Neurol Neuroimmunol Neuroinflamm. 2017 Feb 22;4(3):e334
pubmed: 28255575
Lancet. 2004 Dec 11-17;364(9451):2106-12
pubmed: 15589308
Brain Res. 2015 Mar 10;1600:17-31
pubmed: 25543069
Lancet. 2019 Oct 12;394(10206):1352-1363
pubmed: 31495497
N Engl J Med. 2019 Nov 28;381(22):2114-2124
pubmed: 31774956
J Neurol. 2014 Jan;261(1):1-16
pubmed: 24272588
Nat Rev Neurol. 2018 Oct;14(10):577-589
pubmed: 30171200
Sci Rep. 2018 Oct 4;8(1):14798
pubmed: 30287870
Trends Neurosci. 2020 Jul;43(7):458-466
pubmed: 32423764
Ann Emerg Med. 2012 Jun;59(6):471-83
pubmed: 22071014
Nat Biotechnol. 2010 Jun;28(6):595-9
pubmed: 20495550
J Exp Med. 2005 Aug 15;202(4):473-7
pubmed: 16087714
Neurology. 2020 Jan 28;94(4):e407-e418
pubmed: 31796527
J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1259-1265
pubmed: 29921610
EBioMedicine. 2020 Jun;56:102785
pubmed: 32464528
Neuron. 2018 Oct 24;100(2):375-388
pubmed: 30359603
Nat Genet. 2001 Jan;27(1):117-20
pubmed: 11138011
Tohoku J Exp Med. 2008 May;215(1):55-9
pubmed: 18509235
J Neurol Neurosurg Psychiatry. 2011 Apr;82(4):467-9
pubmed: 20667859
Ann Neurol. 2009 Nov;66(5):630-43
pubmed: 19937948
Lancet Neurol. 2020 Apr;19(4):298-306
pubmed: 32199095