Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica.
BACKGROUND
Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system (CNS) of putative autoimmune aetiology. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. Recently, using indirect immunofluorescence analysis, a new serum autoantibody (NMO-IgG) has been detected in NMO patients. The binding sites of this autoantibody were reported to colocalize with aquaporin 4 (AQP4) water channels. Thus we hypothesized that AQP4 antibodies in fact characterize NMO patients.


RESULTS
Based on these observations we cloned human water channel AQP4, expressed the protein in a eukaryotic transcription/translation system, and employed the recombinant AQP4 to establish a new radioimmunoprecipitation assay (RIPA). Indeed, application of this RIPA showed that antibodies against AQP4 exist in the majority of patients with NMO (n = 37; 21 positive) as well as in patients with isolated longitudinally extensive transverse myelitis (n = 6; six positive), corresponding to a sensitivity of 62.8% and a specificity of 98.3%. By contrast, AQP4 antibodies were virtually absent in 291 other participants, which included patients with MS (n = 144; four positive), patients with other inflammatory and noninflammatory neurological diseases (n = 73; one positive), patients with systemic autoimmune diseases (n = 45; 0 positive), and healthy participants (n = 29; 0 positive).


CONCLUSIONS
In the largest series reported so far to our knowledge, we quantified AQP4 antibodies in patients with NMO versus various other diseases, and showed that the aquaporin 4 water channel is a target antigen in a majority of patients with NMO. The newly developed assay represents a highly specific, observer-independent, and easily reproducible detection method facilitating clinically relevant discrimination between NMO, MS, and other inflammatory diseases.
Paul
Friedemann
F
Cecilie-Vogt-Clinic for Molecular Neurology, Charité, University Medicine Berlin, Berlin, Germany.
Jarius
Sven
S
Aktas
Orhan
O
Bluthner
Martin
M
Bauer
Oliver
O
Appelhans
Heribert
H
Franciotta
Diego
D
Bergamaschi
Roberto
R
Littleton
Edward
E
Palace
Jacqueline
J
Seelig
Hans-Peter
HP
Hohlfeld
Reinhard
R
Vincent
Angela
A
Zipp
Frauke
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000276:immunology; D015531:Radioimmunoprecipitation Assay; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity
D051401:Aquaporin 4; D001323:Autoantibodies; D011994:Recombinant Proteins