Cerebrospinal Fluid Camk2a Levels at Baseline Predict Long-term Progression in Multiple Sclerosis

Overview

Journal Clin Proteomics

Publisher Biomed Central

Date 2023 Aug 29

PMID 37644477

Authors

Dorsa Sohaei

Simon Thebault

Lisa M Avery

Ihor Batruch

Brian Lam

Wei Xu

Rubah S Saadeh

Isobel A Scarisbrick

Eleftherios P Diamandis

Ioannis Prassas

Mark S Freedman

Affiliations

Soon will be listed here.

Abstract

Background: Multiple sclerosis (MS) remains a highly unpredictable disease. Many hope that fluid biomarkers may contribute to better stratification of disease, aiding the personalisation of treatment decisions, ultimately improving patient outcomes.

Objective: The objective of this study was to evaluate the predictive value of CSF brain-specific proteins from early in the disease course of MS on long term clinical outcomes.

Methods: In this study, 34 MS patients had their CSF collected and stored within 5 years of disease onset and were then followed clinically for at least 15 years. CSF concentrations of 64 brain-specific proteins were analyzed in the 34 patient CSF, as well as 19 age and sex-matched controls, using a targeted liquid-chromatography tandem mass spectrometry approach.

Results: We identified six CSF brain-specific proteins that significantly differentiated MS from controls (p < 0.05) and nine proteins that could predict disease course over the next decade. CAMK2A emerged as a biomarker candidate that could discriminate between MS and controls and could predict long-term disease progression.

Conclusion: Targeted approaches to identify and quantify biomarkers associated with MS in the CSF may inform on long term MS outcomes. CAMK2A may be one of several candidates, warranting further exploration.

Citing Articles

Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis.

Wurtz L, Knyazhanskaya E, Sohaei D, Prassas I, Pittock S, Willrich M Clin Proteomics. 2024; 21(1):42.

PMID: 38880880 PMC: 11181608. DOI: 10.1186/s12014-024-09494-5.

Comment on "Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis. Clinical Proteomics".

Dehkordi F, Chehelgerdi M Clin Proteomics. 2023; 20(1):46.

PMID: 37880604 PMC: 10598925. DOI: 10.1186/s12014-023-09433-w.

References

Thebault S, Abdoli M, Fereshtehnejad S, Tessier D, Tabard-Cossa V, Freedman M . Serum neurofilament light chain predicts long term clinical outcomes in multiple sclerosis. Sci Rep. 2020; 10(1):10381. PMC: 7316736. DOI: 10.1038/s41598-020-67504-6. View

Gupta N, Jadhav S, Tan K, Saw G, Mallilankaraman K, Dheen S . miR-142-3p Regulates BDNF Expression in Activated Rodent Microglia Through Its Target CAMK2A. Front Cell Neurosci. 2020; 14:132. PMC: 7253665. DOI: 10.3389/fncel.2020.00132. View

Polman C, Reingold S, Banwell B, Clanet M, Cohen J, Filippi M . Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011; 69(2):292-302. PMC: 3084507. DOI: 10.1002/ana.22366. View

Lublin F, Reingold S, Cohen J, Cutter G, Soelberg Sorensen P, Thompson A . Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83(3):278-86. PMC: 4117366. DOI: 10.1212/WNL.0000000000000560. View

Batruch I, Lim B, Soosaipillai A, Brinc D, Fiala C, Diamandis E . Mass Spectrometry-Based Assay for Targeting Fifty-Two Proteins of Brain Origin in Cerebrospinal Fluid. J Proteome Res. 2020; 19(8):3060-3071. DOI: 10.1021/acs.jproteome.0c00087. View

Liu T, Donahue K, Hu J, Kurnellas M, Grant J, Li H . Identification of differentially expressed proteins in experimental autoimmune encephalomyelitis (EAE) by proteomic analysis of the spinal cord. J Proteome Res. 2007; 6(7):2565-75. PMC: 2430926. DOI: 10.1021/pr070012k. View

Meyer-Moock S, Feng Y, Maeurer M, Dippel F, Kohlmann T . Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis. BMC Neurol. 2014; 14:58. PMC: 3986942. DOI: 10.1186/1471-2377-14-58. View

Yan Z, Chu L, Jia X, Lin L, Cheng S . Myelin basic protein enhances axonal regeneration from neural progenitor cells. Cell Biosci. 2021; 11(1):80. PMC: 8082623. DOI: 10.1186/s13578-021-00584-7. View

Zou Y, Zhang W, Liu H, Li X, Zhang X, Ma X . Structure and function of the contactin-associated protein family in myelinated axons and their relationship with nerve diseases. Neural Regen Res. 2017; 12(9):1551-1558. PMC: 5649478. DOI: 10.4103/1673-5374.215268. View

10.

Gerrard B, Singh V, Babenko O, Gauthier I, Yong V, Kovalchuk I . Chronic mild stress exacerbates severity of experimental autoimmune encephalomyelitis in association with altered non-coding RNA and metabolic biomarkers. Neuroscience. 2017; 359:299-307. DOI: 10.1016/j.neuroscience.2017.07.033. View

11.

Mouton-Barbosa E, Roux-Dalvai F, Bouyssie D, Berger F, Schmidt E, Righetti P . In-depth exploration of cerebrospinal fluid by combining peptide ligand library treatment and label-free protein quantification. Mol Cell Proteomics. 2010; 9(5):1006-21. PMC: 2871408. DOI: 10.1074/mcp.M900513-MCP200. View

12.

Mapstone M, Cheema A, Fiandaca M, Zhong X, Mhyre T, MacArthur L . Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014; 20(4):415-8. PMC: 5360460. DOI: 10.1038/nm.3466. View

13.

Giovannoni G . Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol. 2018; 31(3):233-243. DOI: 10.1097/WCO.0000000000000561. View

14.

Zhang Y, Li D, Zeng Q, Feng J, Fu H, Luo Z . LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis. Mol Med. 2021; 27(1):44. PMC: 8088686. DOI: 10.1186/s10020-021-00304-4. View

15.

Ma X, Zhou J, Zhong Y, Jiang L, Mu P, Li Y . Expression, regulation and function of microRNAs in multiple sclerosis. Int J Med Sci. 2014; 11(8):810-8. PMC: 4057480. DOI: 10.7150/ijms.8647. View

16.

Hashimoto T, Maekawa S, Miyata S . IgLON cell adhesion molecules regulate synaptogenesis in hippocampal neurons. Cell Biochem Funct. 2009; 27(7):496-8. DOI: 10.1002/cbf.1600. View

17.

Kim S, Burette A, Chung H, Kwon S, Woo J, Lee H . NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci. 2006; 9(10):1294-301. DOI: 10.1038/nn1763. View

18.

Sartori A, Abdoli M, Freedman M . Can we predict benign multiple sclerosis? Results of a 20-year long-term follow-up study. J Neurol. 2017; 264(6):1068-1075. DOI: 10.1007/s00415-017-8487-y. View

19.

Munoz-San Martin M, Torras S, Robles-Cedeno R, Buxo M, Gomez I, Matute-Blanch C . Radiologically isolated syndrome: targeting miRNAs as prognostic biomarkers. Epigenomics. 2020; 12(23):2065-2076. DOI: 10.2217/epi-2020-0172. View

20.

Ziemssen T, Kumpfel T, Klinkert W, Neuhaus O, Hohlfeld R . Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Brain. 2002; 125(Pt 11):2381-91. DOI: 10.1093/brain/awf252. View