Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells

Arch Neurol. 2009 Sep;66(9):1164-7. doi: 10.1001/archneurol.2009.188.


Background: Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4)-specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning.

Objective: To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks.

Design, setting, and participants: A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG-seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein-AQP4-transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement.

Main outcome measures: Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer.

Results: The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14% for patients with mild attacks and 54% for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8% and 12%, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089).

Conclusions: A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aquaporin 4 / genetics
  • Aquaporin 4 / immunology*
  • Astrocytes / immunology
  • Biomarkers / analysis
  • Biomarkers / blood
  • Cell Line
  • Child
  • Complement Activation / immunology*
  • Complement System Proteins / immunology*
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Immunoassay / methods*
  • Immunoglobulin G / analysis*
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / diagnosis
  • Neuromyelitis Optica / immunology*
  • Predictive Value of Tests
  • Propidium
  • Retrospective Studies
  • Young Adult


  • AQP4 protein, human
  • Aquaporin 4
  • Biomarkers
  • Immunoglobulin G
  • Green Fluorescent Proteins
  • Propidium
  • Complement System Proteins