MOG-IgG is rare in AQP4-IgG seronegative NMO phenotype in Brazil

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease most frequently characterized by a neuromyelitis optica (NMO) phenotype, comprising both simultaneous or sequential optic neuritis (ON) and longitudinally extensive transverse myelitis (LETM). Symptoms of brainstem, diencephalic and cerebral involvement may also occur. While most NMOSD patients test positive for serum aquaporin-4 (AQP4) antibodies, some seronegative patients test positive for oligodendrocyte glycoprotein-IgG (MOG-IgG). Early identification of seropositive MOG-IgG seropositive patients among those with AQP4-IgG seronegative NMO phenotype may impact disease treatment and outcome. Objective: To determine the frequency of MOG-IgG in patients with AQP4-IgG seronegative NMO phenotype at a single reference center in Brazil and to analyze factors influencing their identification. Methods: A retrospective review of medical records of patients who presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4 antibodies was conducted in a single center in Brazil. Patients were tested for serum AQP4 antibodies and retrospectively for MOG-IgG using cell-based assays. In addition to demographic, clinical, and imaging data, information on time intervals between disease onset and MOG-IgG testing, as well as the most recent relapse to MOG-IgG testing, was collected. Results: Out of 118 patients tested for MOG-IgG, 28 (23.7 %) presented with NMO phenotype and met the 2015 IPND criteria for NMOSD without AQP4-IgG. Three (10.7 %) of them tested positive for MOG-IgG serostatus. All were females and had a median age of 26 (11-34) years at disease presentation. The median disease duration was 11.2 yrs. Two patients had a relapsing course. Optic neuritis, myelitis, and brainstem syndrome were the most common presenting symptoms. The median annualized relapse rate was 0.25, and the median EDSS score at the most recent visit was 2.0 (1.5-5.0). There were 25 double seronegative patients, 21 (84 %) of whom were female and non-Caucasian; the median age at disease onset was 30 years (2-60), and the median EDSS at most recent visit was 4.0 (0 - 8.0). Discussion: The study identified MOG-IgG antibodies in 10.7 % of a cohort with AQP4-IgG seronegative NMO phenotype. Immunosuppressive treatment and long intervals between disease attacks and antibody testing may have impacted the frequency of MOG-IgG seropositivity. As MOG-IgG testing is crucial for diagnosing MOGAD in AQP4-IgG seronegative NMO phenotype, we highlight the need for broader and timely testing to improve diagnostic accuracy in resource-limited settings.