title: Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance.
abstract: BACKGROUND
  In 70-80% of cases, neuromyelitis optica (NMO) is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG). Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO.
  
  
  OBJECTIVE
  To assess the frequency, syndrome specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF) AQP4-Ab in patients with NMO spectrum disorders (NMOSD).
  
  
  METHODS
  87 CSF samples from 37 patients with NMOSD and 42 controls with other neurological diseases were tested for AQP4-Ab in a cell based assay using recombinant human AQP4. Twenty-three paired CSF and serum samples from AQP4-Ab seropositive NMOSD patients were further analysed for intrathecal IgG synthesis to AQP4.
  
  
  RESULTS
  AQP4-Ab were detectable in 68% of CSF samples from AQP4-Ab seropositive patients with NMOSD, but in none of the CSF samples from AQP4-Ab seronegative patients with NMOSD and in none of the control samples. Acute disease relapse within 30 days prior to lumbar puncture, AQP4-Ab serum titres >1:250, and blood-CSF barrier dysfunction, but not treatment status, predicted CSF AQP4-Ab positivity. A positive AQP4-specific antibody index was present in 1/23 samples analysed.
  
  
  CONCLUSIONS
  AQP4-Ab are detectable in the CSF of most patients with NMOSD, mainly during relapse, and are highly specific for this condition. In the cohort analysed in this study, testing for CSF AQP4-Ab did not improve the sensitivity and specificity of the current diagnostic criteria for NMO. The substantial lack of intrathecal AQP4-Ab synthesis in patients with NMOSD may reflect the unique localisation of the target antigen at the blood brain barrier, and is important for our understanding of the immunopathogenesis of the disease.
authors.affiliation: Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Rommer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Reuss
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kristoferitsch
authors.forename: Klaus Peter
authors.initials: KP
authors.lastname: Wandinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000134:cerebrospinal fluid* / Q000276:immunology; D001323:Autoantibodies / Q000134:cerebrospinal fluid* / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid* / Q000276:immunology; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies
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