title: Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders.
abstract: BACKGROUND
  A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation.
  
  
  OBJECTIVE
  In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms.
  
  
  METHODS
  For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) (n = 54), possible CTD (n = 42), or vasculitis (n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4.
  
  
  RESULTS
  AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON (n = 69).
  
  
  CONCLUSIONS
  The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.
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: Christian
authors.initials: C
authors.lastname: Jacobi
authors.forename: Jerome
authors.initials: J
authors.lastname: de Seze
authors.forename: Helene
authors.initials: H
authors.lastname: Zephir
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.forename: Paulus
authors.initials: P
authors.lastname: Rommer
authors.forename: Simone
authors.initials: S
authors.lastname: Mader
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Gulsen
authors.initials: G
authors.lastname: Akman-Demir
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert-Held
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kristoferitsch
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
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; D000369:Aged, 80 and over; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D003240:Connective Tissue Diseases / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009188:Myelitis, Transverse / Q000276:immunology; D009471:Neuromyelitis Optica / Q000276:immunology*; D009902:Optic Neuritis / Q000276:immunology; D012216:Rheumatic Diseases / Q000276:immunology*
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies