Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study

Abstract

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-017-8635-4) contains supplementary material, which is available to authorized users.

International multicenter examination of MOG antibody assays

“…There are limited data on assay reproducibility between these centers. In this study, we compared the most frequently used assays for MOG-IgG detection, such as live and fixed immunofluorescence cell-based assays (CBA-IF), [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] live flow cytometry cell-based assays (CBA-FACS), 4,[18][19][20][21][22][23][24][25][26][27] and ELISA. 28,29…”

The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody

“…This was followed by the use of improved cell-based assay techniques using HEK 293 cells transfected with the correctly folded MOG. MOG-IgG has been shown in multiple studies from independent researchers to be a specific serum biomarker of a subset of central nervous system (CNS) inflammatory demyelinating diseases (IDD), clinically distinct from MS and aquaporin-4 (AQP4) antibody (Ab) seropositive neuromyelitis optica spectrum disorder (NMOSD) [9,29,34,45,51,53,62,63]. Clinical attacks are typically more severe than in MS, with relapses often rendering a patient blind from optic neuritis (ON), wheelchair-dependent from transverse myelitis (TM) or encephalopathic from an ADEM-like presentation [7,15,45].…”

Antibody response against HERV-W in patients with MOG-IgG associated disorders, multiple sclerosis and NMOSD

“…Over the last decade, a spectrum of CNS demyelinating diseases associated with autoantibodies directed against this protein (MOG-IgG) has been characterized (Lopez-Chiriboga et al, 2018). MOG-IgG associated disorders show distinctive clinical and radiological features compared to MS, but frequently overlap those of aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD) (Polman et al, 2011;Wingerchuk et al, 2015;Mariotto et al, 2017). We recently reported an increased humoral immune response towards some antigenic peptides of the HERV-W envelope proteins in MS patients but not in NMOSD patients (either AQP4-IgG positive or double-negative for AQP4-IgG and MOG-IgG), suggesting a possible role for HERV-W antibodies as discriminating biomarker between MS and NMOSD (Arru et al, 2017).…”