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Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine
receptor ?1 subunit in patients with isolated optic neuritis
#MMPMID25506781
Martinez-Hernandez E
; Sepulveda M
; Rostásy K
; Höftberger R
; Graus F
; Harvey RJ
; Saiz A
; Dalmau J
JAMA Neurol
2015[Feb]; 72
(2
): 187-93
PMID25506781
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IMPORTANCE: In patients with isolated optic neuritis (ON), the presence of
antibodies to aquaporin 4 (AQP4) has diagnostic and prognostic value. In the same
clinical setting, the significance of antibodies to myelin-oligodendrocyte
glycoprotein (MOG) or the glycine receptor ?1 subunit (GlyR) is unclear.
OBJECTIVES: To investigate the frequency of antibodies to AQP4, MOG, and GlyR in
patients with unilateral or bilateral, severe, or recurrent isolated ON and to
determine their clinical and prognostic correlates. DESIGN, SETTING, AND
PARTICIPANTS: Retrospective case-control study from November 1, 2005, through May
30, 2014 with the detection of autoantibodies in a neuroimmunology referral
center. We included 51 patients with ON but without clinical and magnetic
resonance imaging findings outside the optic nerves and 142 controls (30 healthy
individuals, 48 patients with neuromyelitis optica, and 64 patients with multiple
sclerosis). MAIN OUTCOMES AND MEASURES: Clinicoimmunologic analysis. We
determined the presence of antibodies to AQP4, MOG, and GlyR using cell-based
assays. RESULTS: The median age of the patients at the onset of ON symptoms was
28 (range, 5-65) years; 36 patients (71%) were female. Antibodies were identified
in 23 patients (45%), including MOG in 10 patients, AQP4 in 6 patients, and GlyR
in 7 patients (concurrent with MOG in 3 and concurrent with AQP4 in 1). Patients
with AQP4 antibodies (median visual score, 3.5 [range, 1-9]) had a worse visual
outcome than patients with MOG antibodies alone (median visual score, 0 [range,
0-5]; P?=?.007), patients with seronegative findings (n?=?28) (median visual
score, 1.0 [range, 0-14]; P?=?.08), and patients with GlyR antibodies alone
(n?=?3) (median visual score, 0 [range, 0-2]; P?=?.10).The median age of the 7
patients with GlyR antibodies was 27 (range, 11-38) years; 5 (71%) of these were
female. Among the 3 patients with GlyR antibodies alone, 1 patient had monophasic
ON, 1 had recurrent isolated ON, and 1 had conversion to multiple sclerosis. The
3 patients with GlyR antibodies concurrent with MOG antibodies had recurrent
isolated ON, and the patient with concurrent AQP4 antibodies had conversion to
neuromyelitis optica. Of the 48 controls with neuromyelitis optica, 37 (77%) had
AQP4 antibodies, 4 (8%) had MOG antibodies, 2 (4%) had AQP4 antibodies concurrent
with MOG antibodies, and 5 (10%) were seronegative. Of the 64 controls with
multiple sclerosis, 5 (8%) had GlyR antibodies. CONCLUSIONS AND RELEVANCE:
Forty-five percent of patients with unilateral or bilateral, severe, or recurrent
isolated ON had antibodies to MOG, AQP4, or GlyR. Patients with AQP4 antibodies
had the poorest visual outcomes, whereas patients with MOG antibodies had a
better outcome that was similar to that of patients with seronegative findings.
The significance of GlyR antibodies in the setting of ON is unclear and deserves
further study.
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