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


METHODS
Case-control study.


METHODS
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%.
McKeon
Andrew
A
Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Fryer
James P
JP
Apiwattanakul
Metha
M
Lennon
Vanda A
VA
Hinson
Shannon R
SR
Kryzer
Thomas J
TJ
Lucchinetti
Claudia F
CF
Weinshenker
Brian G
BG
Wingerchuk
Dean M
DM
Shuster
Elizabeth A
EA
Pittock
Sean J
SJ
D000328:Adult; D051401:Aquaporin 4 / Q000032:analysis* / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007150:Immunohistochemistry / Q000379:methods* / Q000706:statistics & numerical data; D047468:Immunoprecipitation / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D009188:Myelitis, Transverse / Q000175:diagnosis / Q000276:immunology; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000276:immunology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D051401:Aquaporin 4; D007074:Immunoglobulin G; D049452:Green Fluorescent Proteins