An international multicenter examination of MOG antibody assays

Abstract

Objectives: To compare the reproducibility of 11 antibody assays for IgG and IgM myelin oligodendrocyte glycoprotein antibodies (MOG-IgG, MOG-IgM) from five international centers. Methods: The following samples were analyzed: MOG-IgG clearly positive sera (n=39), MOG-IgG low positive sera (n=39), borderline negative sera (n=13), clearly negative sera (n=40), and healthy blood donors (n=30). As technical controls, 18 replicates (9 MOG-IgG positive and 9 negative) were included. All samples and controls were re-coded, aliquoted, and distributed to the five testing centers which performed the following antibody assays: five live and one fixed immunofluorescence cell-based assays (CBA-IF, five MOG-IgG, one MOG-IgM), three live flow cytometry cell-based assays (FACS-CBA, all MOG-IgG), and two enzyme-linked immunosorbent assays (ELISA, both MOG-IgG). Results: We found excellent agreement (96%) between the live CBAs for MOG-IgG for samples previously identified as clearly positive or negative from four different national testing centers. The agreement was lower with fixed CBA-IF (90%) and the ELISA showed no concordance with CBAs for detection of human MOG-IgG. All CBAs showed excellent inter-assay reproducibility. The agreement of MOG-IgG CBAs for borderline negative (77%) and particularly low positive (33%) samples was less good. Finally, most samples from healthy blood donors (97%) were negative for MOG-IgG in all CBAs. Conclusion: Live MOG-IgG CBAs showed excellent agreement for high positive and very good agreement for negative samples at four international testing centers. Low positive samples were more frequently discordant than in similar assays for other autoantigens. Further research is needed to improve international standardization for clinical care.

Longitudinally extensive transverse myelitis with anti-myelin oligodendrocyte glycoprotein antibodies following SARS-CoV-2 infection

“…There are only two other cases of myelitis following SARS-CoV-2 infection associated with MOG-IgG: one case of bilateral optic neuritis and LETM, and a multifocal mid-thoracic spinal cord myelitis and HHV6 coinfection/reactivation which confounds interpretation of the clinical findings ( Jumah et al, 2020 ; Zhou et al, 2020 ). Furthermore, MOG-IgG was not determined by cell based assay in these cases, and thus laboratory significance of the finding is unknown ( Reindl et al, 2020 ; Reindl and Waters, 2019 ).…”

AQP4-IgG-seronegative patient outcomes in the N-MOmentum trial of inebilizumab in neuromyelitis optica spectrum disorder

“…Few AQP4− patients with clinical characteristics of NMOSD have been identified as having detectable serum concentration of antibodies against MOG, a protein expressed on the outer surface of the myelin sheath and oligodendrocytes (Kitley et al, 2012;Mader et al, 2011;Reindl et al, 2020). Multiple clinical, histopathological, and laboratory investigations demonstrated that patients with AQP4−/MOG+ NMOSD have a different underlying pathogenesis from patients with AQP4+ NMOSD (Borisow et al, 2018;Kim et al, 2020;Marignier et al, 2013;Zamvil & Slavin, 2015).…”

Time to Disability Milestones and Annualized Relapse Rates in NMOSD and MOGAD

“…A diagnosis of NMOSD without AQP4-IgG additionally required documented negative testing for MOG-IgG (AQP4-IgG À /MOG-IgG À NMOSD). Standard testing for AQP4-IgG and MOG-IgG was performed with cell-based assays 27,28 in the majority of the patients (at least 70% in AQP4-IgG + NMOSD and 82% in MOGAD, for the rest no documentation of assay available). Patients were excluded in case of incomplete core data sets or absence of at least one documented EDSS examination in stable disease phase without relation to an attack.…”