title: Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor α1 subunit in patients with isolated optic neuritis.
abstract: OBJECTIVE
  In patients with isolated optic neuritis (ON), the presence of antibodies to aquaporin 4 (AQP4) has diagnostic and prognostic value. In the same clinical setting, the significance of antibodies to myelin-oligodendrocyte glycoprotein (MOG) or the glycine receptor α1 subunit (GlyR) is unclear.
  
  
  OBJECTIVE
  To investigate the frequency of antibodies to AQP4, MOG, and GlyR in patients with unilateral or bilateral, severe, or recurrent isolated ON and to determine their clinical and prognostic correlates.
  
  
  METHODS
  Retrospective case-control study from November 1, 2005, through May 30, 2014 with the detection of autoantibodies in a neuroimmunology referral center. We included 51 patients with ON but without clinical and magnetic resonance imaging findings outside the optic nerves and 142 controls (30 healthy individuals, 48 patients with neuromyelitis optica, and 64 patients with multiple sclerosis).
  
  
  METHODS
  Clinicoimmunologic analysis. We determined the presence of antibodies to AQP4, MOG, and GlyR using cell-based assays.
  
  
  RESULTS
  The median age of the patients at the onset of ON symptoms was 28 (range, 5-65) years; 36 patients (71%) were female. Antibodies were identified in 23 patients (45%), including MOG in 10 patients, AQP4 in 6 patients, and GlyR in 7 patients (concurrent with MOG in 3 and concurrent with AQP4 in 1). Patients with AQP4 antibodies (median visual score, 3.5 [range, 1-9]) had a worse visual outcome than patients with MOG antibodies alone (median visual score, 0 [range, 0-5]; P = .007), patients with seronegative findings (n = 28) (median visual score, 1.0 [range, 0-14]; P = .08), and patients with GlyR antibodies alone (n = 3) (median visual score, 0 [range, 0-2]; P = .10).The median age of the 7 patients with GlyR antibodies was 27 (range, 11-38) years; 5 (71%) of these were female. Among the 3 patients with GlyR antibodies alone, 1 patient had monophasic ON, 1 had recurrent isolated ON, and 1 had conversion to multiple sclerosis. The 3 patients with GlyR antibodies concurrent with MOG antibodies had recurrent isolated ON, and the patient with concurrent AQP4 antibodies had conversion to neuromyelitis optica. Of the 48 controls with neuromyelitis optica, 37 (77%) had AQP4 antibodies, 4 (8%) had MOG antibodies, 2 (4%) had AQP4 antibodies concurrent with MOG antibodies, and 5 (10%) were seronegative. Of the 64 controls with multiple sclerosis, 5 (8%) had GlyR antibodies.
  
  
  CONCLUSIONS
  Forty-five percent of patients with unilateral or bilateral, severe, or recurrent isolated ON had antibodies to MOG, AQP4, or GlyR. Patients with AQP4 antibodies had the poorest visual outcomes, whereas patients with MOG antibodies had a better outcome that was similar to that of patients with seronegative findings. The significance of GlyR antibodies in the setting of ON is unclear and deserves further study.
authors.affiliation: Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Martinez-Hernandez
authors.affiliation: Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Sepulveda
authors.affiliation: Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain3Division of Pediatric Neurology, Department of Pediatrics IV, Innsbruck Medical University, Innsbruck, Austria4Pediatric Neurology, Children's Ho.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostásy
authors.affiliation: Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain5Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.affiliation: Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.affiliation: Department of Pharmacology, UCL School of Pharmacy, London, England.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.affiliation: Department of Neurology, Hospital Clínic, University of Barcelona, Barcelona, Spain2Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Neuroimmunology Program, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain7Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D009902:Optic Neuritis / Q000175:diagnosis / Q000276:immunology*; D011379:Prognosis; D018009:Receptors, Glycine / Q000276:immunology*; D012008:Recurrence; D055815:Young Adult
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D063308:Myelin-Oligodendrocyte Glycoprotein; D018009:Receptors, Glycine