Review Article | Published:

Myelin oligodendrocyte glycoprotein antibodies in neurological disease

Nature Reviews Neurology (2018) | Download Citation

Abstract

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease.

Key points

  • Antibodies against myelin oligodendrocyte glycoprotein (MOG-Abs) that are detectable with cell-based assays are associated with non-MS acquired demyelinating syndromes of the CNS.

  • MOG-Ab-associated disorders account for a larger proportion of paediatric patients than that of adult patients who present with acquired demyelinating disease.

  • The clinical presentation of MOG-Ab-associated disorders changes with age: MOG-Abs are associated with an ADEM-like presentation in young children and an opticospinal presentation in children aged >9 years and adults.

  • Most patients with MOG-Ab-associated disorders have favourable outcomes, but a subset are left with permanent disability, usually as a result of the initial attack.

  • Many patients develop relapsing disease; relapses usually involve optic neuritis and often occur during steroid weaning or soon after steroid cessation, suggesting that a longer initial treatment duration is required.

  • Investigation of human MOG-Ab pathogenicity is hampered by their limited binding to rodent MOG; nevertheless, the place of MOG-Ab-associated disorders in the spectrum of inflammatory demyelinating diseases is becoming clearer.

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Acknowledgements

The research of M.R. is supported by research grants from the Austrian Federal Ministry of Science, Research and Education (grant BIG WIG MS, Markus Reindl), the Austrian Research promotion Agency (FFG, Bridge 1 project Nr. 853209 EDNA), the Austrian Science Funds (FWF, project W1206) and the Austrian Multiple Sclerosis Research Society. Research in the laboratory of P.W. is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK and the NIHR Oxford Biomedical Research Centre, UK.

Reviewer information

Nature Reviews Neurology thanks J. de Seze, M. Levy, S. Pittock and the other anonymous reviewers for their contribution to the peer review of this work.

Review criteria

We searched PubMed for original articles that were published between 1990 and 2018 and focused on anti-MOG antibodies in neurological diseases. We used the search terms “myelin oligodendrocyte glycoprotein”, “MOG”, “antibodies”, “autoantibodies”, “cell based assay”, “immunofluorescence”, “flow cytometry”, “multiple sclerosis”, “acute disseminated encephalomyelitis”, “neuromyelitis optica”, “optic neuritis” and “myelitis” alone and in combination. All articles identified were English-language, full-text papers. We also searched the reference lists of identified articles for further relevant papers. For the summaries of study results, only studies in which there were more than 10 patients per group were included.

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  1. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    • Markus Reindl
  2. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    • Patrick Waters

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Contributions

Both authors contributed equally to researching data for the article, discussion of the content, writing, and reviewing and/or editing of the manuscript before submission.

Competing interests

The University Hospital and Medical University of Innsbruck (Austria; M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). P.W. is a named inventor on patents for antibody assays and has received royalties. He has received honoraria and/or consulting fees from Biogen, Euroimmun, Mereo Biopharma and Retrogenix, and has received travel grants from the Guthy-Jackson Charitable Foundation. He has received research funding from Euroimmun.

Corresponding author

Correspondence to Markus Reindl.

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https://doi.org/10.1038/s41582-018-0112-x