Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

Abstract

Objective:We examined a cohort of adults with aquaporin-4 (AQP4) antibody–negative neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD) for antibodies to myelin oligodendrocyte glycoprotein (MOG).Methods:We performed a flow cytometry cell-based assay using live human lentivirus–transduced cells expressing full-length surface MOG. Serum was tested in 23 AQP4 antibody–negative NMO/NMOSD patients with bilateral and/or recurrent optic neuritis (BON, n = 11), longitudinally extensive transverse myelitis (LETM, n = 10), and sequential BON and LETM (n = 2), as well as in patients with multiple sclerosis (MS, n = 76) and controls (n = 52).Results:MOG antibodies were detected in 9/23 AQP4 antibody–negative patients with NMO/NMOSD, compared to 1/76 patients with MS and 0/52 controls (p < 0.001). MOG antibodies were detected in 8/11 patients with BON, 0/10 patients with LETM, and 1/2 patients with sequential BON and LETM. Six of 9 MOG antibody–positive patients had a relapsing course. MOG antibody–positive patients had prominent optic disc swelling and were more likely to have a rapid response to steroid therapy and relapse on steroid cessation than MOG antibody–negative patients (p = 0.034 and p = 0.029, respectively). While 8/9 MOG antibody–positive patients had good follow-up visual acuity, one experienced sustained visual impairment, 3 had retinal nerve fiber layer thinning, and one had residual spinal disability.Conclusions:MOG antibodies have a strong association with BON and may be a useful clinical biomarker. MOG antibody–associated BON is a relapsing disorder that is frequently steroid responsive and often steroid dependent. Failure to recognize the disorder early and institute immunotherapy promptly may be associated with sustained impairment.Classification of evidence:This study provides Class II evidence that MOG antibodies are associated with AQP4 antibody–negative BON (sensitivity 69%, 95% confidence interval [CI] 42%–87%; specificity 99%, 95% CI 93.7%–99.8%).