Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis.
BACKGROUND
Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord.


OBJECTIVE
To assess the frequency of AQP4-Ab in patients with optic neuritis (ON), and to investigate the prognostic implications of AQP4-Ab seropositivity in such patients.


METHODS
AQP4-Ab serum levels were determined in 224 individuals from Austria, Denmark, France, Germany, Italy, and Turkey using a newly developed fluorescence immunoprecipitation assay employing recombinant human AQP4.


RESULTS
AQP4-Ab were detectable in 8/139 (5.8%) patients with acute monosymptomatic optic neuritis (AMON) and in 10/17 (58.8%) patients with established NMO and a last relapse of acute ON (NMO/ON), but not in 32 patients with multiple sclerosis or in 36 healthy controls. At last examination, 4/8 (50%) seropositive AMON patients had met the criteria for NMO but 0/128 seronegative AMON patients. Disease severity differed significantly between seropositive and seronegative AMON. Complete bilateral or unilateral blindness occurred in six AQP4-Ab positive patients, but only in one AQP4-Ab negative patient. AQP4-Ab levels did not vary between seropositive AMON and NMO/ON and did not correlate with disease severity. Female gender, a relapsing course, and concomitant autoimmunity were associated with AQP4-Ab seropositive status and risk of developing NMO.


CONCLUSIONS
AQP4-Ab is relatively rare among patients with AMON, but if present it predicts a high rate of conversion to NMO within one year.
Jarius
Sven
S
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Frederikson
Jette
J
Waters
Patrick
P
Paul
Friedemann
F
Akman-Demir
Gulsen
G
Marignier
Romain
R
Franciotta
Diego
D
Ruprecht
Klemens
K
Kuenz
Bettina
B
Rommer
Paulus
P
Kristoferitsch
Wolfgang
W
Wildemann
Brigitte
B
Vincent
Angela
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000906:Antibodies / Q000097:blood*; D051401:Aquaporin 4 / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000453:epidemiology / Q000473:pathology; D009902:Optic Neuritis / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D012737:Sex Factors; D016896:Treatment Outcome; D055815:Young Adult
D000906:Antibodies; D051401:Aquaporin 4