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  • Review Article
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Body fluid biomarkers for multiple sclerosis—the long road to clinical application

Nature Reviews Neurology volume 11, pages 585–596 (2015)Cite this article

Subjects

Key Points

  • Blood and cerebrospinal fluid biomarkers can assist early diagnosis of multiple sclerosis (MS) and help predict conversion from clinically isolated syndrome to MS

  • Body fluid biomarkers are also essential in differential diagnosis of neuromyelitis optica

  • Prognostic evaluation of MS is currently challenging, but novel axonal damage markers, including neurofilments and N-acetylaspartate, could be implemented in biomarker panels to improve their predictive power

  • Despite rapidly increasing number of disease-modifying treatments, few body fluid biomarkers are available to monitor treatment response and predict adverse effects

  • No clinically implemented biomarkers are available for MS subtyping and staging; IgM oligoclonal bands and microRNAs are the most promising candidates

  • International collaboration for standardized assays and study protocols, as well as to recruit sufficiently large cohorts, can facilitate biomarker development

Abstract

There is a strong unmet clinical need for objective body fluid biomarkers to assist early diagnosis and estimate long-term prognosis, monitor treatment response and predict potential adverse effects in multiple sclerosis (MS). Here, we review recent studies (focusing on 2012 to early 2015) on body fluid markers in MS from the perspective of their clinical utility. Because the first step towards clinical implementation of a newly discovered biomarker is independent replication, we focus on biomarkers that have been validated in at least two independent cohorts. We also discuss recent data challenging earlier findings, and biomarkers for which new clinical uses are suggested. For early MS diagnosis and prediction of conversion from clinically isolated syndrome to MS, several new B-cell-associated candidate blood biomarkers have emerged. For prognosis, several novel axonal damage markers should be adopted to biomarker panels. The number of disease-modifying treatments for MS has increased sharply, but biomarkers for treatment response monitoring and adverse effect prediction are scarce, and markers for subtyping and staging of MS are still lacking. In view of the availability and implementation of several standardized protocols to optimize biomarker studies, we expect biomarker development for MS to be improved and accelerated, with clinical implementation in the near future.

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Figure 1: Biomarkers associated with different clinical phases in MS.
Figure 2: Schematic representation of the process of biomarker development.

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Acknowledgements

We acknowledge support from the Dutch MS Research Foundation (grant no 14-358e “Facing MS progression”), Fonds NutsOhra (grant no. ZonMw 89000005) and the International Progressive MS Alliance.

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Authors and Affiliations

  1. Department of Clinical Chemistry, Neurochemistry Laboratory and Biobank, Neuroscience Campus Amsterdam, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, Netherlands

    Charlotte E. Teunissen & Arjan Malekzadeh

  2. Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, Netherlands

    Cyra Leurs & Joep Killestein

  3. Department of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva University Hospital, Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland

    Claire Bridel

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  1. Charlotte E. Teunissen
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  4. Claire Bridel
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  5. Joep Killestein
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Contributions

All authors provided substantial contribution to discussion of content of the article, and contributed to researching data for the article, and writing, reviewing and editing the article.

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Correspondence to Charlotte E. Teunissen.

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Competing interests

C.E.T. serves on the advisory board of Fujirebio and Roche, has received research consumables from Fujirebio, Euroimmun, IBL, Invitrogen and Mesoscale Discovery, and has performed contract research for Boehringer, IBL, Probiodrug, Roche and Shire. J.K. has received consulting and speaker fees from Biogen, Genzyme, Novartis, Merck-Serono and TEVA. The VUMC MS Center Amsterdam has received financial support for research activities from Bayer Schering Pharma, Biogen Idec, Genzyme, Glaxo Smith Kline, Merck Serono, Novartis, and Teva. The other authors declare no competing interests.

Supplementary information

Supplementary Table 1

Summary of discussed studies on biomarkers for predicting conversion to MS and MS diagnosis (DOCX 94 kb)

Supplementary Table 2

Summary of discussed studies for differential diagnosis of MS and NMO (DOCX 41 kb)

Supplementary Table 3

Summary of discussed studies on biomarkers for subtyping and prognosis of MS (DOCX 48 kb)

Supplementary Table 4

Summary of discussed studies on biomarkers for treatment response in the period 2012–2015 (DOCX 51 kb)

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Teunissen, C., Malekzadeh, A., Leurs, C. et al. Body fluid biomarkers for multiple sclerosis—the long road to clinical application. Nat Rev Neurol 11, 585–596 (2015). https://doi.org/10.1038/nrneurol.2015.173

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