Advertisement

Oligoclonal M bands unveil occult inflammation in multiple sclerosis

Published:August 15, 2022DOI:https://doi.org/10.1016/j.msard.2022.104118

      Abstract

      Introduction

      Recent works demonstrate that patients with multiple sclerosis (pwMS) and oligoclonal M bands (OCMB) in cerebrospinal fluid (CSF) are at higher risk of conversion to secondary progressive course, suggesting a distinct pathophysiology pathway in these patients.

      Objectives

      To analyze the relationship of serum neurofilament light chain (s-NFL) in absence of inflammatory activity in people with multiple sclerosis (pwMS) according to the presence of OCMB versus healthy controls (HC), and the effect of aging.

      Methods

      Two cohorts of HC were compared to a cohort of pwMS without clinical or radiological signs of acute inflammation. Lack of inflammation was defined as the absence of relapses or gadolinium-enhancing lesions (GEL) brain in an MRI performed within three months before and after s-NFL determination. S-NFL was measured with SIMOa technology. OCMB in the cerebrospinal fluid (CSF) were analyzed with isoelectric focusing and immunoblotting.

      Results

      254 people were studied: 124 healthy voluntary controls and 130 pwMS. Despite the absence of inflammatory activity, pwMS and OCMB showed higher levels of s-NFL compared to those without OCMB and HC (11.4 pg/mL, 8.9 pg/mL and 9.0 pg/mL, respectively). A positive and exponential correlation between age and s-NFL was observed, with highest increases among pwMS and OCMB in the CSF.

      Discussion

      In absence of overt inflammatory activity, pwMS and OCMB exhibit higher s-NFL levels, and a greater age-related increase. Thus, OCMB may portray an underlying inflammatory process not detected by conventional MRI studies and may explain the poorer prognosis of these patients.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Abdo W.F.
        • van de Warrenburg B.P.C.
        • Munneke M.
        • et al.
        CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia.
        Neurology. 2006; 67: 474-479https://doi.org/10.1212/01.wnl.0000227891.25592.8c
        • Benkert P.
        • Meier S.
        • Schaedelin S.
        • et al.
        Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study.
        Lancet Neurol. 2022; 21: 246-257https://doi.org/10.1016/S1474-4422(22)00009-6
        • Blennow K.
        • Hampel H.
        • Weiner M.
        • Zetterberg H.
        Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.
        Nat. Rev. Neurol. 2010; 6: 131-144https://doi.org/10.1038/nrneurol.2010.4
        • Barro C.
        • Benkert P.
        • Disanto G.
        • et al.
        Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis.
        Brain : J. Neurol. 2018; 141: 2382-2391https://doi.org/10.1093/brain/awy154
        • Disanto G.
        • Barro C.
        • Benkert P.
        • et al.
        Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis.
        Ann. Neurol. 2017; 81: 857-870https://doi.org/10.1002/ana.24954
        • Gresle M.M.
        • Butzkueven H.
        • Shaw G.
        Neurofilament proteins as body fluid biomarkers of neurodegeneration in multiple sclerosis.
        Mult. Scler. Int. 2011; 2011: 1-7https://doi.org/10.1155/2011/315406
        • Hendricks R.
        • Baker D.
        • Brumm J.
        • et al.
        Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood.
        Bioanalysis. 2019; 11: 1405-1418https://doi.org/10.4155/bio-2019-0163
        • Khalil M.
        • Pirpamer L.
        • Hofer E.
        • et al.
        Serum neurofilament light levels in normal aging and their association with morphologic brain changes.
        Nat. Commun. 2020; 11: 812https://doi.org/10.1038/s41467-020-14612-6
        • Kuhle J.
        • Barro C.
        • Andreasson U.
        • et al.
        Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa.
        Clin. Chem. Lab. Med. 2016; 54: 1655-1661https://doi.org/10.1515/cclm-2015-1195
        • Kuhle J.
        • Nourbakhsh B.
        • Grant D.
        • et al.
        Serum neurofilament is associated with progression of brain atrophy and disability in early MS.
        Neurology. 2017; 88: 826-831https://doi.org/10.1212/WNL.0000000000003653
        • Lleó A.
        • Alcolea D.
        • Martínez-Lage P.
        • et al.
        Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer’s disease continuum in the BIOMARKAPD study.
        Alzheimers Dement. 2019; 15: 742-753https://doi.org/10.1016/j.jalz.2019.01.015
        • Magraner M.J.
        • Bosca I.
        • Sim??-Castell?? M.
        • et al.
        Brain atrophy and lesion load are related to CSF lipid-specific IgM oligoclonal bands in clinically isolated syndromes.
        Neuroradiology. 2012; 54: 5-12https://doi.org/10.1007/s00234-011-0841-7
        • Monreal E.
        • Sainz de la Maza S.
        • Costa-Frossard L.
        • et al.
        Predicting aggressive multiple sclerosis with intrathecal IgM synthesis among patients with a clinically isolated syndrome.
        Neurol. Neuroimmunol. neuroinflam. 2021; 8: 1-11https://doi.org/10.1212/NXI.0000000000001047
        • Novakova L.
        • Zetterberg H.
        • Sundström P.
        • et al.
        Monitoring disease activity in multiple sclerosis using serum neurofilament light protein.
        Neurology. 2017; 89: 2230-2237https://doi.org/10.1212/WNL.0000000000004683
        • Oechtering J.
        • Lincke T.
        • Schaedelin S.
        • et al.
        Intrathecal IgM synthesis is associated with spinal cord manifestation and neuronal injury in early MS.
        Ann. Neurol. 2022; : 0-3https://doi.org/10.1002/ana.26348
        • Petzold A.
        • Steenwijk M.D.
        • Eikelenboom J.M.
        • et al.
        Elevated CSF neurofilament proteins predict brain atrophy: a 15-year follow-up study.
        Mult. Scler. 2016; 22: 1154-1162https://doi.org/10.1177/1352458516645206
        • Rissin D.M.
        • Kan C.W.
        • Campbell T.G.
        • et al.
        Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations.
        Nat. Biotechnol. 2010; 28: 595-599https://doi.org/10.1038/nbt.1641
        • Teunissen C.E.
        • Khalil M.
        Neurofilaments as biomarkers in multiple sclerosis.
        Mult. Scler. 2012; 18: 552-556https://doi.org/10.1177/1352458512443092
        • Villar L.M.
        • González-Porqué P.
        • Masjuán J.
        • et al.
        A sensitive and reproducible method for the detection of oligoclonal IgM bands.
        J. Immunol. Methods. 2001; 258: 151-155https://doi.org/10.1016/S0022-1759(01)00492-6
        • Yilmaz A.
        • Blennow K.
        • Hagberg L.
        • et al.
        Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.
        Expert Rev. Mol. Diagn. 2017; 17: 761-770https://doi.org/10.1080/14737159.2017.1341313