Chen, John J.

Objective The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG‐IgG) testing. Methods We retrospectively identified patients for CSF MOG‐IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG‐IgG for testing including: controls, 282; serum MOG‐IgG positive MOG antibody‐associated disease (MOGAD), 74; serum MOG‐IgG negative high‐risk phenotypes, 73; serum false positive MOG‐IgG with alternative diagnoses, 18. A live cell‐based assay assessed CSF MOG‐IgG positivity (IgG‐binding‐index [IBI], ≥2.5) using multiple anti‐human secondary antibodies and end‐titers were calculated if sufficient sample volume. Correlation of CSF MOG‐IgG IBI and titer was assessed. Results The pan‐IgG Fc‐specific secondary was optimal, yielding CSF MOG‐IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG‐IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG‐IgG positive MOGAD patients; and 9/73 (12%) serum MOG‐IgG negative patients with high‐risk phenotypes. Serum negative but CSF positive MOG‐IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG‐IgG low‐positives revealed CSF MOG‐IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG‐IgG (3/15[20%]) ( p = 0.01). CSF MOG‐IgG IBI and CSF MOG‐IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001). Interpretation CSF MOG‐IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG‐IgG, and those with low positive serum MOG‐IgG results and diagnostic uncertainty. These findings support a role for CSF MOG‐IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34–45

Abstract: Monoclonal antibody therapies mark the new era of targeted treatment for relapse prevention in aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD). For over a decade, rituximab, an anti-CD20 B-cell-depleting agent, had been the most effectiveness treatment for AQP4-IgG+NMOSD. Tocilizumab, an anti-interleukin-6 receptor, was also observed to be effective. In 2019, several randomized, placebo-controlled trials were completed that demonstrated the remarkable efficacy of eculizumab (anti-C5 complement inhibitor), inebilizumab (anti-CD19 B-cell-depleting agent), and satralizumab (anti-interleukin-6 receptor), leading to the Food and Drug Administration (FDA) approval of specific treatments for AQP4-IgG+NMOSD for the first time. Most recently, ravulizumab (anti-C5 complement inhibitor) was also shown to be highly efficacious in an open-label, external-controlled trial. Although only some patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) warrant immunotherapy, there is currently no FDA-approved treatment for relapse prevention in MOGAD. Observational studies showed that tocilizumab was associated with a decrease in relapses, whereas rituximab seemed to have less robust effectiveness in MOGAD compared to AQP4-IgG+NMOSD. Herein, we review the evidence on the efficacy and safety of each monoclonal antibody therapy used in AQP4-IgG+NMOSD and MOGAD, including special considerations in children and women of childbearing potential.