Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton

Russell C. Dale, Esther M. Tantsis, Vera Merheb, Raani Yogeeta A. Kumaran, Nese Sinmaz, Karrnan Pathmanandavel, Sudarshini Ramanathan, David R. Booth, Louise A. Wienholt, Kristina Prelog, Damien R. Clark, Gilles J. Guillemin, Chai K. Lim, Emily K. Mathey, Fabienne Brilot*

*Corresponding author for this work

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Abstract

OBJECTIVE: To examine the clinical features of pediatric CNS demyelination associated with positive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects of MOG antibody on oligodendrocyte cytoskeleton.

METHODS: We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3-15.3) followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on oligodendrocyte cytoskeleton using 3D deconvolution imaging.

RESULTS: MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first presentation, MOG antibody-positive patients were more likely to have bilateral than unilateral optic neuritis (ON) (9/10 vs 1/5, respectively, p = 0.03), less likely to have brainstem findings (2/31 vs 16/42, p = 0.005), more likely to have a raised erythrocyte sedimentation rate >20 mm/h (9/19 vs 3/21, p = 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p = 0.18), and less likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, p = 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON most likely to be seropositive. Two relapsing MOG antibody-positive patients treated with mycophenolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes incubated with purified IgG from MOG antibody-positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and β-tubulin immunolabelings.

CONCLUSIONS: MOG antibody may define a separate demyelination syndrome, which has therapeutic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton.

Original languageEnglish
Article numbere12
Pages (from-to)1-12
Number of pages12
JournalNeurology: Neuroimmunology and Neuroinflammation
Volume1
Issue number1
DOIs
Publication statusPublished - 24 Apr 2014

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Copyright the Author(s) 2014. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Dale, R. C., Tantsis, E. M., Merheb, V., Kumaran, R. Y. A., Sinmaz, N., Pathmanandavel, K., ... Brilot, F. (2014). Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurology: Neuroimmunology and Neuroinflammation, 1(1), 1-12. [e12]. https://doi.org/10.1212/NXI.0000000000000012