title: A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.
abstract: BACKGROUND
  Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis.
  
  
  METHODS
  Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity.
  
  
  RESULTS
  NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease.
  
  
  CONCLUSIONS
  NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.
authors.affiliation: Department of Neurology, Mayo Clinic Rochester, Rochester, MN 55905, USA. lennon.vanda@mayo.edu
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wingerchuk
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kryzer
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis*; D009471:Neuromyelitis Optica / Q000175:diagnosis*; D009902:Optic Neuritis / Q000175:diagnosis; D012008:Recurrence; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G