title: MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin.
abstract: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders.
  
  
  
  To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers.
  
  
  
  614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells.
  
  
  
  MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 %) patients with a history of both ON and myelitis, 22/103 (21.4 %) with a history of ON but no myelitis and 6/45 (13.3 %) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 %) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 %) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment.
  
  
  
  To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.
authors: Molecular Neuroimmunology Group, Otto Meyerhof Center, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
authors: Sven
authors: S
authors: Jarius
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Klemens
authors: K
authors: Ruprecht
authors: Department of Neurology, Ruhr University Bochum, Bochum, Germany.
authors: Ingo
authors: I
authors: Kleiter
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine, Charité University Medicine Berlin, Berlin, Germany.
authors: Nadja
authors: N
authors: Borisow
authors: Department of Neurology and Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors: Nasrin
authors: N
authors: Asgari
authors: Department of Neurology, Ruhr University Bochum, Bochum, Germany.
authors: Kalliopi
authors: K
authors: Pitarokoili
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine, Charité University Medicine Berlin, Berlin, Germany.
authors: Florence
authors: F
authors: Pache
authors: Department of Neurology, Albert Ludwigs University, Freiburg, Germany.
authors: Oliver
authors: O
authors: Stich
authors: Department of Neurology, Albert Ludwigs University, Freiburg, Germany.
authors: Lena-Alexandra
authors: LA
authors: Beume
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Martin W
authors: MW
authors: Hümmert
authors: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors: Corinna
authors: C
authors: Trebst
authors: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
authors: Marius
authors: M
authors: Ringelstein
authors: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
authors: Orhan
authors: O
authors: Aktas
authors: Department of Neurology, University of Rostock, Rostock, Germany.
authors: Alexander
authors: A
authors: Winkelmann
authors: Department of Neurology, Julius Maximilians University, Würzburg, Germany.
authors: Mathias
authors: M
authors: Buttmann
authors: Molecular Neuroimmunology Group, Otto Meyerhof Center, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany.
authors: Alexander
authors: A
authors: Schwarz
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Hanna
authors: H
authors: Zimmermann
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Alexander U
authors: AU
authors: Brandt
authors: IRCCS, C. Mondino National Neurological Institute, Pavia, Italy.
authors: Diego
authors: D
authors: Franciotta
authors: Centro di Riferimento Regionale SM, Azienda Ospedaliero Universitaria San Luigi Gonzaga, Orbassano, Italy.
authors: Marco
authors: M
authors: Capobianco
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Joseph
authors: J
authors: Kuchling
authors: Molecular Neuroimmunology Group, Otto Meyerhof Center, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany.
authors: Jürgen
authors: J
authors: Haas
authors: Molecular Neuroimmunology Group, Otto Meyerhof Center, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany.
authors: Mirjam
authors: M
authors: Korporal-Kuhnke
authors: Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
authors: Soeren Thue
authors: ST
authors: Lillevang
authors: Institute of Experimental Immunology, affiliated to Euroimmun AG, Lübeck, Germany.
authors: Kai
authors: K
authors: Fechner
authors: Clinical Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors: Kathrin
authors: K
authors: Schanda
authors: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine, Charité University Medicine Berlin, Berlin, Germany.
authors: Friedemann
authors: F
authors: Paul
authors: Molecular Neuroimmunology Group, Otto Meyerhof Center, Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany.
authors: Brigitte
authors: B
authors: Wildemann
authors: Clinical Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
authors: Markus
authors: M
authors: Reindl
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology*; D009187:Myelitis / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000097:blood* / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology; D012720:Severity of Illness Index; D014162:Transfection
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Antibody index; Aquaporin-4 antibodies (AQP4-IgG); Autoantibodies; Cell-based assays; Cerebrospinal fluid; Devic’s syndrome; Longitudinally extensive transverse myelitis (LETM); Multiple sclerosis; Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); Neuromyelitis optica antibodies (NMO-IgG); Neuromyelitis optica spectrum disorders (NMOSD); Neuromyelitis optica (NMO); Optic neuritis; Transverse Myelitis