title: Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity.
abstract: OBJECTIVE
  To optimize aquaporin-4 (AQP4) antibody (Ab) detection and to assess the influence of the increased sensitivity of the assay on the demographic and disease-related characteristics of a group of AQP4-Ab-negative patients.
  
  
  METHODS
  Serum samples were obtained from patients included in the French NOMADMUS database with a definite diagnosis of neuromyelitis optica (NMO) (n = 87) and were compared with controls (n = 54). They were tested by indirect immunofluorescence and cell-based assays (CBAs) in various conditions and with several plasmids.
  
  
  RESULTS
  We identified the CBA on live cells transfected with the untagged AQP4-M23 isoform as the best method, with a sensitivity of 74.4% and a specificity of 100%. We demonstrated a direct relationship between improvement of the sensitivity of the detection method and the distinctiveness and characteristics of the AQP4-Ab-negative NMO group. Whereas with the classic indirect immunofluorescence or current AQP4-M1 CBA we found only slight differences between the 2 populations, using the AQP4-M23 CBA, we demonstrated that patients with AQP4-Ab-negative NMO expressed specific demographic and disease-related features. They were characterized by an equal male/female ratio (p < 0.001), a Caucasian ethnicity (p = 0.029), and an overrepresentation of simultaneous optic neuritis and transverse myelitis at first episode (p = 0.015). In terms of disability, they experienced a better visual acuity at last follow-up compared with seropositive NMO (p = 0.007).
  
  
  CONCLUSIONS
  This raises the question of a distinct physiopathology for patients with AQP4-Ab-negative NMO and of their place in the spectrum of the disease.
authors: Lyon's Neuroscience Research Center, Team ONCOFLAM, Inserm U 1028/CNRS 5292, Lyon, France. romain.marignier@chu-lyon.fr
authors: Romain
authors: R
authors: Marignier
authors: Raphaël
authors: R
authors: Bernard-Valnet
authors: Pascale
authors: P
authors: Giraudon
authors: Nicolas
authors: N
authors: Collongues
authors: Caroline
authors: C
authors: Papeix
authors: Hélène
authors: H
authors: Zéphir
authors: Gaëlle
authors: G
authors: Cavillon
authors: Véronique
authors: V
authors: Rogemond
authors: Romain
authors: R
authors: Casey
authors: Bernard
authors: B
authors: Frangoulis
authors: Jérôme
authors: J
authors: De Sèze
authors: Sandra
authors: S
authors: Vukusic
authors: Jérôme
authors: J
authors: Honnorat
authors: Christian
authors: C
authors: Confavreux
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000592:standards; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000276:immunology*; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D015415:Biomarkers