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Collateral benefit: the comeback of MOG antibodies as a biomarker in neurological practice
  1. Orhan Aktas
  1. Department of Neurology, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
  1. Correspondence to Dr Orhan Aktas, Department of Neurology, Heinrich-Heine-University, Moorenstr. 5, Düsseldorf D-40225, Germany; orhan.aktas{at}uni-duesseldorf.de

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In childhood acute disseminated encephalomyelitis antibodies to myelin oligodendrocyte glycoprotein are associated with a marked inflammatory phenotype

In autoimmune central nervous system (CNS) disorders the identification of biomarkers related to the aberrant immune response is an important research aim with a potentially huge impact on clinical practice. As a recent example neuromyelitis optica (NMO) may be considered where the usage of antibodies against the astrocytic aquaporin-4 (AQP4) water channel as a biomarker leads to better defined patient cohorts, helps investigating and predicting the disease course, improves our understanding of disease pathogenesis, and, finally, facilitates tailored clinical trials.

Remarkably, for multiple sclerosis (MS) as the most common chronic neuroimmunological disease in Western countries, the establishment of such a biomarker has been difficult. This is reflected by the rise and fall of antibodies recognising the self-antigen candidate myelin oligodendrocyte glycoprotein (MOG), localised on the surface of CNS myelin sheets. Initially such anti-MOG antibodies were suggested to predict the disease course after the onset of relapsing MS but this finding could not be verified thereafter. Follow-up investigations revealed the technical challenges of MOG antibody detection1: Western blot and ELISA applied in early studies rather identify antibodies to denaturated MOG whereas the detection of antibodies to correctly folded MOG protein requires advanced methodology such as cell-based assays (CBA) or tetramer technology.

Of note, while the relevance of MOG antibodies still remains disputed in MS, recent studies using improved assays uncovered MOG-IgG in other neuroinflammatory conditions, including childhood acute disseminating encephalomyelitis (ADEM).2 However, possible clinical implications of this observation remained open so far. Now, in the paper by Baumann et al,3 the authors provide a prospective and comprehensive study, covering clinical, radiological and laboratory follow-up in a cohort of 33 paediatric patients with ADEM with and without MOG-IgG. What are the lessons to be learned from this paper?

The main message is the contrasting presentation of ADEM according to MOG-IgG serostatus (defined by an established CBA). At onset more than half of the patients (58%) were seropositive and characterised by an overall stronger inflammatory phenotype as compared to the seronegative subgroup. MOG-IgG seropositive patients had a higher cerebrospinal fluid cell count, a distinct MRI pattern (characterised by larger and predominantly bilateral hemispheric lesions with fuzzy lesion borders and a more frequent affection of the brain stem/spinal cord), as well as a better clinical and radiological recovery on immunosuppressive relapse therapy. On follow-up, a minor patient subgroup (12% of the cohort) experienced further inflammatory events such as another ADEM episode or optic neuritis, and all of them were seropositive for MOG-IgG at initial ADEM onset.

Taken together, the present study reflects the remarkable comeback of MOG antibodies to the clinical stage, relevant for both the acute and the long-term management of paediatric ADEM. Children with ADEM should be tested for MOG-IgG using state-of-the-art assays, and MOG-IgG seropositive patients with ADEM should be closely monitored for further events. Considering the presence of MOG-IgG in paediatric and adult AQP4-seronegative NMO,4 ,5 further studies will have to address the conversion of MOG-seropositive ADEM to NMO spectrum disorders and possible therapeutic implications.

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Footnotes

  • Funding OA received grants by the German Research Foundation (DFG), the Hertie Foundation, the Eugène Devic European Network (EU-FP7), German Ministry for Education and Research (BMBF), Schaufler Foundation, and Walter-and-Ilse-Rose Stiftung; and research support by Bayer Schering, Biogen Idec, Novartis and Teva.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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