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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton
Russell C Dale1, Esther M Tantsis1, Vera Merheb1
1Neuroimmunology Group (R.C.D., E.M.T., V.M., R.-Y.A.K., N.S., K. Pathmanandavel, S.R., F.B.), Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, Sydney Medical School, University of Sydney, Westmead, Australia; Institute for Immunology and Allergy Research (D.R.B.), Westmead Millenium Institute for Medical Research, University of Sydney, Westmead, Australia; Clinical Immunology (L.A.W.), Royal Prince Alfred Hospital, Sydney Medical School Immunology & Infectious Diseases, University of Sydney, Camperdown, Australia; Department of Radiology (K. Prelog), the Children's Hospital at Westmead, Australia; Department of Paediatric Neurology (D.R.C.), Women's and Children's Hospital, North Adelaide, Australia; Neuroinflammation Group (G.J.G., C.K.L.), MND and Neurodegenerative Diseases Research Centre, Macquarie University, Australian School of Advanced Medicine, North Ryde, Australia; and Neuroinflammation Group (E.K.M.), Brain and Mind Research Institute, University of Sydney, Camperdown, Australia.
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.
Insights
Myelin oligodendrocyte glycoprotein (MOG) antibodies are linked to pediatric central nervous system (CNS) demyelination, potentially defining a distinct syndrome. These MOG antibodies impact the oligodendrocyte cytoskeleton, suggesting therapeutic implications.
Area of Science:
- Neuroimmunology
- Pediatric Neurology
- Demyelinating Diseases
Background:
- Pediatric central nervous system (CNS) demyelination is a group of disorders.
- Myelin oligodendrocyte glycoprotein (MOG) antibodies are implicated in some cases.
- Understanding the clinical features and pathogenic mechanisms is crucial.
Purpose of the Study:
- To characterize the clinical presentation of pediatric CNS demyelination associated with MOG antibodies.
- To investigate the functional impact of MOG antibodies on oligodendrocyte cytoskeleton.
Main Methods:
- Assessed MOG antibodies in 73 children with CNS demyelination using live cell-based assays.
- Utilized MO3.13 cells and 3D imaging to analyze IgG effects on oligodendrocyte cytoskeleton.
Main Results:
- MOG antibodies detected in 42% of pediatric CNS demyelination cases.
- MOG antibody-positive patients showed higher rates of bilateral optic neuritis and lower rates of brainstem involvement.
- Patient-derived MOG IgG disrupted oligodendrocyte cytoskeleton organization.
Conclusions:
- MOG antibody positivity may identify a distinct demyelinating syndrome in children.
- MOG antibodies exert functional effects on the oligodendrocyte cytoskeleton.
- This finding has potential therapeutic implications for MOG antibody-associated demyelination.
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