Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor α1 subunit in patients with isolated optic neuritis

Abstract

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 α1 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.

Figure. Identification of Antibodies (Ab) to the Glycine Receptor α1 Subunit (GlyR) Concurrent With Aquaporin 4 (AQP4) Ab or Myelin-Oligodendrocyte Glycoprotein (MOG) Antibodies

We transfected HEK293 cells with GlyR (row 1), the full-length MOG C-terminal fused to enhanced green fluorescent protein (EGFP; row 2), and the AQP4-M23 isoform (row 3). Column 1 shows the serum immunostaining; column 2, commercial Abs to GlyR and AQP4 in red and MOG-EGFP–expressing cells in green; and column 3, merged reactivities and the nuclei of the cells revealed with 4',6-diamidino-2-phenylindole (DAPI). A, Serum from patient 1 shows reactivity with GlyR- and MOG-transfected cells (rows 1 and 2) but not with AQP4-transfected cells (row 3). B, Serum from patient 5 shows reactivity with GlyR- and AQP4-transfected cells (rows 1 and 3) but not with MOG-transfected cells (row 2). C, In contrast, serum from a control individual yields negative findings on all 3 transfected cells (rows 1–3).