title: Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the presence of antibodies to conformation-intact myelin oligodendrocyte glycoprotein (MOG) in a subgroup of adult patients with clinically definite multiple sclerosis (MS) preselected for a specific clinical phenotype including severe spinal cord, optic nerve, and brainstem involvement.
  
  
  METHODS
  Antibodies to MOG were investigated using a cell-based assay in 3 groups of patients: 104 preselected patients with MS (group 1), 55 age- and sex-matched, otherwise unselected patients with MS (group 2), and in 22 brain-biopsied patients with demyelinating diseases of the CNS (n = 19 with MS), 4 of whom classified as MS type II (group 3). Recognized epitopes were identified with mutated variants of MOG.
  
  
  RESULTS
  Antibodies to MOG were found in about 5% (5/104) of preselected adult patients with MS. In contrast, in groups 2 and 3, none of the patients tested positive for MOG antibodies. Patients with MS with antibodies to MOG predominantly manifested with concomitant severe brainstem and spinal cord involvement and had a severe disease course with high relapse rates and failure to several disease-modifying therapies. Three of them had been treated with plasma exchange with a favorable response. All anti-MOG-positive patients with MS showed typical MS lesions on brain MRI. Longitudinal analysis up to 9 years revealed fluctuations and reappearance of anti-MOG reactivity. Epitope mapping indicated interindividual heterogeneity, yet intraindividual stability of the antibody response.
  
  
  CONCLUSIONS
  Antibodies to MOG can be found in a distinct subgroup of adult MS with a specific clinical phenotype and may indicate disease heterogeneity.
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Melania
authors.initials: M
authors.lastname: Spadaro
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Lisa Ann
authors.initials: LA
authors.lastname: Gerdes
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ertl-Wagner
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Franziska Sabrina
authors.initials: FS
authors.lastname: Thaler
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schuh
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Blaschek
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dick
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
authors.affiliation: Institute of Clinical Neuroimmunology (M.S., L.A.G., M.K., F.S.T., E.S., R.H., E.M., T.K.), Department of Radiology (B.E.-W.), and Laboratory for Immunogenetics (A.D.), Medical Campus Großhadern, Ludwig-Maximilians-Universität München; Department of Neurology (M.K.), Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen; Department of Neuropathology (I.M., W.B.), University Medical Center, Georg August University, Göttingen; Department of Paediatric Neurology and Developmental Medicine (A.B.), Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Munich, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel