Diagnosis of neuromyelitis spectrum disorders: comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays

Arch Neurol. 2009 Sep;66(9):1134-8. doi: 10.1001/archneurol.2009.178.


Objective: To compare the sensitivity and specificity of immunofluorescence (IF) and immunoprecipitation (IP) assays using green fluorescent protein-tagged aquaporin-4 (AQP4) in 6335 patients for whom serological evaluation was requested on a service basis.

Design: Case-control study.

Setting: Mayo Clinic Neuroimmunology Laboratory (Rochester, Minnesota) and Departments of Neurology (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida). Patients Group 1, 835 Mayo Clinic patients, 100 with a neuromyelitis optica (NMO) spectrum disorder diagnosis and 735 without NMO spectrum disorder; group 2, 5500 non-Mayo Clinic patients. Main Outcome Measure Sensitivity and specificity of each assay for NMO or NMO spectrum disorder, individually and combined.

Results: In group 1, the sensitivity rates for NMO were IF, 58%; IP, 33%; and combined assays, 63%. The sensitivity rates for relapsing longitudinally extensive transverse myelitis were IF, 29%; IP, 6%; and combined assays, 29%. The specificity rates for NMO and relapsing longitudinally extensive transverse myelitis were IF, 99.6%; IP, 99.3%; and combined assays, 99.2%. In group 2, NMO-IgG was detected by IF in 498 of 5500 patients (9.1%) and by IP in 331 patients (6.0%); 76 of the 331 patients seropositive by IP (23%) were negative by IF. Clinical information was available for 124 patients (including 16 of those seropositive by IP only); 123 had a definite NMO spectrum disorder and 1 was at risk for NMO (monophasic optic neuritis).

Conclusions: In this large, clinical practice-based study, NMO-IgG detected by IF or IP was highly specific for NMO spectrum disorders. The IP assay was significantly less sensitive than IF. Combined testing improved sensitivity by 5%.

Publication types

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

MeSH terms

  • Adult
  • Aquaporin 4 / analysis*
  • Aquaporin 4 / blood
  • Aquaporin 4 / immunology
  • Case-Control Studies
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Immunoglobulin G / analysis
  • Immunoglobulin G / blood
  • Immunohistochemistry / methods*
  • Immunohistochemistry / statistics & numerical data
  • Immunoprecipitation / methods*
  • Immunoprecipitation / statistics & numerical data
  • Male
  • Myelitis, Transverse / diagnosis
  • Myelitis, Transverse / immunology
  • Neuromyelitis Optica / diagnosis*
  • Neuromyelitis Optica / immunology
  • Predictive Value of Tests
  • Sensitivity and Specificity


  • Aquaporin 4
  • Immunoglobulin G
  • Green Fluorescent Proteins