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Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration

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Abstract

Antibodies against conformation-dependent epitopes of myelin-oligodendrocyte-glycoprotein (MOG-abs) are present in subgroups of neuromyelitis optica spectrum disorder (NMOSD), recurrent optic neuritis (rON), multiple sclerosis (MS), and anti-NMDAR encephalitis. Using optical coherence tomography (OCT) we assessed whether MOG-abs might serve as potential marker of retinal axonal degeneration. We investigated a clinically heterogeneous cohort of 13 MOG-abs-positive patients (4 MOG-abs-positive rON, 4 MOG-abs-positive adult MS, 3 MOG-abs-positive relapsing encephalomyelitis, 2 MOG-abs-positive aquaporin-4-abs-negative NMOSD). As controls, we studied 13 age, sex and ON episode(s)-matched MOG-abs and aquaporin-4-abs-negative (AQP4-abs-negative) MS patients and 13 healthy controls (HC). In addition, we investigated 19 unmatched AQP4-abs-positive MOG-abs-negative NMOSD subjects. Considering all eyes, global pRNFL [in µm, mean (SD)] was significantly reduced in MOG-abs-positive patients [72.56 (22.71)] compared to MOG-abs-negative MS [80.81 (13.55), p = 0.0128], HCs [103.54 (8.529), p = 0.0014] and NMOSD [88.32 (18.43), p = 0.0353]. Non ON eyes from MOG-abs-positive subjects showed significant subclinical atrophy of temporal pRNFL quadrants. Microcystic macular edema (MME) was observed only in eyes of MOG-abs-positive (24%) and AQP4-abs-positive NMOSD (5.6%), but not in MOG-abs-negative MS or HC (p < 0.01). MOG-abs may serve as potential marker of retinal degeneration. Specifically, MOG-abs-related OCT features predominate in temporal pRNFL quadrants (resembling the MS retinal pattern), might be more severe than AQP4-abs-positive NMOSD, indicate subclinical pathology, and may be associated with MME.

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Acknowledgements

We are grateful to Dr. F. Thaler and Dr. S. Liebscher for helpful comments on the manuscript. We thank A. Bamberger for technical support.

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Correspondence to Joachim Havla.

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JH received speaker honoraria, travel expenses, and personal compensations from Merck, Biogen, Bayer-Healthcare, Sanofi Genzyme and Novartis Pharma. TK has received travel expenses and speaking honoraria from Bayer-Healthcare, Genzyme, Teva-Pharma, Merck, Novartis-Pharma, Sanofi, and Biogen and grant support from Bayer-Schering AG and Novartis-Pharma. RS, MS and ES have nothing to disclose. EM has received grant support from Novartis-Pharma and personal compensations from Roche. RH is supported by the Deutsche Forschungsgemeinschaft, Munich Cluster for Systems Neurology (SYNERGY) and the KKNMS and has received personal compensations from Bayer-Healthcare, Teva-Pharma, Merck, Biogen, Novartis-Pharma, Sanofi and Genzyme. OO reports grant for research from Novartis-Pharma; grants and personal fees from Biogen, Genzyme, Merck, Novartis-Pharma and Teva-Pharma, outside the submitted work.

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The study was approved by the local ethics committee (Ethikkommission bei der LMU München, 427-14) in compliance with the Declaration of Helsinki. All patients and HC gave written consent to participate in the study.

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415_2016_8333_MOESM1_ESM.tif

Suppl Fig. MOG-abs testing by a cell-based flow cytometric assay; anti-MOG IgG (MFI ratio) in MOG-abs-positive patients (N=12) vs. MOG-abs-negative MS cohort (N=13), cut off 2.27 (MFI, mean fluorescence intensity), the dashed line indicates the cutoff for anti-MOG positivity (TIFF 372 kb)

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Havla, J., Kümpfel, T., Schinner, R. et al. Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration. J Neurol 264, 139–151 (2017). https://doi.org/10.1007/s00415-016-8333-7

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