title: Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton.
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.
authors.affiliation: Neuroimmunology 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.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.affiliation: Neuroimmunology 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.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Tantsis
authors.affiliation: Neuroimmunology 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.
authors.forename: Vera
authors.initials: V
authors.lastname: Merheb
authors.affiliation: Neuroimmunology 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.
authors.forename: Raani-Yogeeta A
authors.initials: RY
authors.lastname: Kumaran
authors.affiliation: Neuroimmunology 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.
authors.forename: Nese
authors.initials: N
authors.lastname: Sinmaz
authors.affiliation: Neuroimmunology 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.
authors.forename: Karrnan
authors.initials: K
authors.lastname: Pathmanandavel
authors.affiliation: Neuroimmunology 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.
authors.forename: Sudarshini
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Neuroimmunology 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.
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
authors.affiliation: Neuroimmunology 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.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Wienholt
authors.affiliation: Neuroimmunology 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.
authors.forename: Kristina
authors.initials: K
authors.lastname: Prelog
authors.affiliation: Neuroimmunology 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.
authors.forename: Damien R
authors.initials: DR
authors.lastname: Clark
authors.affiliation: Neuroimmunology 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.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.affiliation: Neuroimmunology 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.
authors.forename: Chai K
authors.initials: CK
authors.lastname: Lim
authors.affiliation: Neuroimmunology 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.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Mathey
authors.affiliation: Neuroimmunology 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.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot