Filippatou, Angeliki

Abstract Objective To assess the real‐world performance of a live (LCBA) versus a fixed (FCBA) cell‐based assay for the detection of serum antibodies directed against myelin oligodendrocyte glycoprotein (MOG‐IgG) and aquaporin‐4 (AQP4‐IgG). Methods This was a retrospective study of patients evaluated at a single tertiary academic referral center, with serum testing performed clinically for AQP4‐IgG and/or MOG‐IgG by FCBA and LCBA on the same day. Additionally, frozen banked sera from the same day for patients tested only by one assay were retrieved and tested by the other assay. FCBA was performed by the Johns Hopkins Immunology Laboratory using Euroimmun kits with detection by indirect immunofluorescence (FCBA‐IF), whereas LCBA was performed by the Mayo Clinic Neuroimmunology Laboratory with detection by flow cytometry (LCBA‐FACS). Results Of 594 specimens with paired MOG‐IgG testing, 500 were negative by both assays, 33 were positive by both assays, 56 were positive exclusively by LCBA‐FACS, and 5 were only positive by FCBA‐IF. Overall, MOG‐IgG LCBA‐FACS exhibited 95.1% sensitivity and 97.7% specificity, whereas MOG‐IgG FCBA‐IF had 45.7% sensitivity and 99.8% specificity. Of 577 specimens with paired AQP4‐IgG testing, 503 were negative by both assays, 51 were positive by both assays, 21 were positive exclusively by LCBA‐FACS, and 2 were only positive by FCBA‐IF. Overall, AQP4‐IgG LCBA‐FACS exhibited 97.3% sensitivity and 100% specificity, whereas AQP4‐IgG FCBA‐IF had 71.6% sensitivity and 100% specificity. Interpretation LCBA‐FACS for both MOG‐IgG and AQP4‐IgG had markedly better sensitivity than FCBA‐IF, with similar specificity. The use of FCBA‐IF may result in underrecognition of both MOG antibody‐associated disease (MOGAD) and AQP4‐IgG seropositive neuromyelitis optica spectrum disorder (NMOSD).

ObjectivePatients with myelin oligodendrocyte glycoprotein antibody (MOG‐IgG)‐associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro‐axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON‐independent retinal atrophy can be detected in MOGAD.MethodsEighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high‐definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified.ResultsAt baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD‐ON) compared with MOGAD eyes without a history of ON (MOGAD‐NON) and HCs (p < 0.001). MOGAD‐NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow‐up up to 3 years), MOGAD‐ON with ON within the last 6–12 months before baseline exhibited greater pRNFL thinning than MOGAD‐ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort.InterpretationOur study suggests the absence of attack‐independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476–485