Antiacquaporin 4 antibodies detection by different techniques in neuromyelitis optica patients.
BACKGROUND
Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as a marker for the diagnosis of neuromyelitis optica (NMO). However, a consensus on seroprevalence and optimal detection method has not yet been reached.


OBJECTIVE
To investigate the performance of different assays to detect anti-AQP4 antibodies.


METHODS
We set up five different assays. Two of them were capable to detect perivascular IgG reactivity on brain tissue by immunofluorescence (NMO-IgG). Other three assays have been set to detect anti-AQP4 antibodies: immunofluorescence and flow cytometry on AQP4-expressing cells, and a radioimmunoprecipitation assay. We assessed sensitivity and specificity of these assays by interrogating sera of 33 NMO patients, 13 patients at high risk to develop NMO (hrNMO), 6 patients affected by acute partial transverse myelitis (APTM), 20 patients with multiple sclerosis (MS), and 67 age- and sex-matched healthy controls.


RESULTS
We found that the presence of serum NMO-IgG and anti-AQP4 reactivity is almost exclusively restricted to patients with NMO and hrNMO. Seroprevalence and sensitivity ranged from 30 to 47%, depending on the assay. Specificity ranged from 95 to 100%. Comparing results obtained in the five assays, we noticed lack of concordance in some samples.


CONCLUSIONS
Detection of NMO-IgG or anti-AQP4 antibodies may represent a valuable tool to assist neurologists in the differential diagnosis between patients with NMO, hrNMO, APTM, or MS. The current lack of a gold standard to detect anti-AQP4 antibodies implies the necessity to standardize the detection of these antibodies.
Fazio
R
R
Institute of Experimental Neurology (INSpe), Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
Malosio
M L
ML
Lampasona
V
V
De Feo
D
D
Privitera
D
D
Marnetto
F
F
Centonze
D
D
Ghezzi
A
A
Comi
G
G
Furlan
R
R
Martino
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D001921:Brain / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology; D009188:Myelitis, Transverse / Q000175:diagnosis / Q000276:immunology; D009471:Neuromyelitis Optica / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D015531:Radioimmunoprecipitation Assay; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016036:Seroepidemiologic Studies; D055815:Young Adult
C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G