Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders.

autoimmune encephalitis (AE) autoimmune neurological disorders biomarker cerebellar ataxia neurofilament (NF) neurofilament light (NfL) chain

Journal

Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899

Informations de publication

Date de publication:
2022
Historique:
received: 01 04 2021
accepted: 01 02 2022
entrez: 21 3 2022
pubmed: 22 3 2022
medline: 22 3 2022
Statut: epublish

Résumé

To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE). Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs. Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls. Twenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND ( Our findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.

Sections du résumé

Objective UNASSIGNED
To evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE).
Background UNASSIGNED
Each particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs.
Design/Methods UNASSIGNED
Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls.
Results UNASSIGNED
Twenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND (
Conclusions UNASSIGNED
Our findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.

Identifiants

pubmed: 35309573
doi: 10.3389/fneur.2022.689975
pmc: PMC8924486
doi:

Types de publication

Journal Article

Langues

eng

Pagination

689975

Informations de copyright

Copyright © 2022 Kammeyer, Mizenko, Sillau, Richie, Owens, Nair, Alvarez, Vollmer, Bennett and Piquet.

Déclaration de conflit d'intérêts

RK has received compensation for advisory boards and consultancy with Genentech/Roche. EA has received compensation for activities such as advisory boards, lectures and consultancy with the following companies and organizations: Actelion/Janssen, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono/Merck, Genentech/Roche, Genzyme. EA has received research support from the following: Biogen, Genentech/Roche, Novartis, TG Therapeutics, Patient-Centered Outcomes Research Initiative, National Multiple Sclerosis Society, National Institutes of Health, and Rocky Mountain MS Center. KN has received grant funding from Genentech and Novartis and consulting fees from Novartis, Biogen, and Bristol Meyers Squibb. TV has received compensation for lectures and consultancy from Biogen, Genentech/Roche, Siranax, Celgene, EMD Serono and Novartis and has received research support from Rocky Mountain Multiple Sclerosis Center, Celgene, Biogen, Anokion, Genentech, F. Hoffmann-La Roche Ltd, GW Pharma and TG Therapeutics, Inc. JB reports personal fees from Roche, personal fees from Genentech, personal fees from Viela Bio, personal fees from Chugai Pharma, personal fees from Alexion, grants and personal fees from Novartis, personal fees from Genzyme, personal fees from Clene Nanoscience, personal fees from Mitsubishi-Tanabe, personal fees from Reistone Bio, grants from National Institutes of Health, outside the submitted work. JB has a patent Aquaporumab issued. AP has received research funding from the Drake Family, Rocky Mountain MS Center, and the University of Colorado through the intradepartmental grant. Outside of this work, AP reports honorarium from MedLink and consulting fees from Genentech/Roche and Alexion. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Lancet Neurol. 2013 Feb;12(2):157-65
pubmed: 23290630
J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):12-20
pubmed: 26296871
Eur J Neurol. 2016 Apr;23(4):796-806
pubmed: 26822123
J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):402-4
pubmed: 9527161
Neuron. 2016 Jul 20;91(2):494-496
pubmed: 27477021
J Neuroimmunol. 2017 May 15;306:25-30
pubmed: 28385184
Neurology. 2018 Oct 2;91(14):e1338-e1347
pubmed: 30217937
Neurology. 2020 Aug 11;95(6):e610-e622
pubmed: 32641538
Neurology. 2016 May 3;86(18):1655-6
pubmed: 27037233
JAMA Neurol. 2021 Nov 1;78(11):1333-1344
pubmed: 34542573
Neuron. 2016 Jul 6;91(1):1-3
pubmed: 27387643
JAMA Neurol. 2014 Jul 1;71(7):896-900
pubmed: 24842754
Sci Rep. 2020 Jun 25;10(1):10381
pubmed: 32587320
Ann Neurol. 2016 Jan;79(1):152-8
pubmed: 26528863
J Neurol. 2019 Jul;266(7):1643-1648
pubmed: 30944980
Mult Scler Relat Disord. 2021 Sep;54:103090
pubmed: 34182224
Neurology. 2019 Jan 15;92(3):e244-e252
pubmed: 30578370
Neurol Neuroimmunol Neuroinflamm. 2017 Nov 28;5(1):e422
pubmed: 29209636
Neurology. 2020 Aug 11;95(6):e623-e636
pubmed: 32641529
Mult Scler. 2018 Jul;24(8):1046-1054
pubmed: 28627962
Front Neurol. 2018 Sep 19;9:668
pubmed: 30283395
Neurology. 2020 Jun 9;94(23):e2412-e2423
pubmed: 32461282
Ann Clin Transl Neurol. 2016 Jul 01;3(8):623-36
pubmed: 27606344
Brain. 2018 Feb 1;141(2):348-356
pubmed: 29272336
Sci Transl Med. 2021 Sep 29;13(613):eabg9922
pubmed: 34586833
Neurology. 2016 May 3;86(18):1683-91
pubmed: 27037228
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
Ann Neurol. 2018 Jan;83(1):166-177
pubmed: 29293273

Auteurs

Ryan Kammeyer (R)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Christopher Mizenko (C)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Stefan Sillau (S)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Alanna Richie (A)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Gregory Owens (G)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Kavita V Nair (KV)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Department of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Enrique Alvarez (E)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Timothy L Vollmer (TL)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Jeffrey L Bennett (JL)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Amanda L Piquet (AL)

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Classifications MeSH