Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity

Neurology. 2013 Jun 11;80(24):2194-200. doi: 10.1212/WNL.0b013e318296e917. Epub 2013 May 8.


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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aquaporin 4 / immunology*
  • Autoantibodies* / blood
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Cohort Studies
  • Databases, Factual
  • Female
  • Fluorescent Antibody Technique, Indirect / standards
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neuromyelitis Optica / diagnosis*
  • Neuromyelitis Optica / immunology*
  • Young Adult


  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • Biomarkers