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. 2022 Oct;28(11):1697-1709.
doi: 10.1177/13524585221093789. Epub 2022 May 17.

Serum MOG-IgG in children meeting multiple sclerosis diagnostic criteria

Giulia Fadda  1 , Patrick Waters  2 , Mark Woodhall  2 , Robert A Brown  3 , Julia O'Mahony  4 , Denise A Castro  5 , Giulia Longoni  6 , E Ann Yeh  6 , Ruth Ann Marrie  7 , Douglas L Arnold  8 , Brenda Banwell  9 , Amit Bar-Or  10
Affiliations

Serum MOG-IgG in children meeting multiple sclerosis diagnostic criteria

Giulia Fadda et al. Mult Scler. 2022 Oct.

Abstract

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is now recognized as distinct from multiple sclerosis (MS).

Objective: To evaluate the importance of considering myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin-G (IgG) serology when applying MS diagnostic criteria in children.

Methods: Within a prospective cohort of children meeting MS criteria (median follow-up = 6 years, interquartile range (IQR) = 4-9), we measured MOG-IgG in serial archived serum obtained from presentation, and compared imaging and clinical features between seropositive and seronegative participants.

Results: Of 65 children meeting MS criteria (median age = 14.0 years, IQR = 10.9-15.1), 12 (18%) had MOG-IgG at disease onset. Seropositive participants were younger, had brain magnetic resonance imaging (MRI) features atypical for MS, rarely had cerebrospinal fluid (CSF) oligoclonal bands (2/8, 25%), and accumulated fewer T2 lesions over time. On serial samples, 5/12 (42%) were persistently seropositive, 5/12 (42%) became seronegative, and 2/12 (17%) had fluctuating results. All 12 children experienced a disease course different from typical MS.

Conclusion: While children with MOG-IgG can have clinical, CSF, and MRI features conforming to MS criteria, the presence of MOG-IgG is associated with atypical features and predicts a non-MS disease course. Given MOG-IgG seropositivity can wane over time, testing at first attack is of considerable importance for the diagnosis of MOGAD.

Keywords: All demyelinating diseases (CNS); MRI; all pediatric; autoimmune diseases; multiple sclerosis.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: G.F., M.W., J.O.M., D.A.C., and G.L. report no disclosures. P.W. and the University of Oxford hold patents for antibody assays and receive royalties. He has received speaker honoraria from Alexion, Roche, and UBC. He is co-director of Oxford Autoimmune Diagnostic Laboratory where MOG-IgG testing is performed. R.A.B. is the founder and president of ShadowLab Research Inc. and has provided advisory services or received personal compensation for consulting from NeuroRx Research, Biogen Idec, and the Population Council. D.L.A. reports personal fees for consulting from Acorda, Biogen, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, GeNeuro, MedImmune, Merck-Serono, Novartis, and Sanofi-Aventis; grants from Biogen, Immunotec, and Novartis; and an equity interest in NeuroRx Research. R.A.M. receives research funding from: CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, and US Department of Defense. She is supported by the Waugh Family Chair in Multiple Sclerosis. She is a co-investigator on studies funded by Biogen Idec and Roche. E.A.Y. reports personal fees for consulting from Biogen, F. Hoffmann-La Roche, and Alexion; grants from Biogen, Ontario Institute for Regenerative Medicine, Stem Cell Network, Centre for Brain and Mental Health, The Peterson Foundation, National MS Society, MS Scientific Foundation, National Institutes of Health, Canadian Institutes of Health Research, and Consortium of MS Centers. B.B. receives funding from the Multiple Sclerosis Scientific Foundation, and the National Multiple Sclerosis Society. She has received consultancy fees from Novartis, UCB pharmaceuticals, and Medscape. She serves as a non-remunerated advisor on clinical trial design for Novartis, Biogen, Teva Neuroscience, and Sanofi-Aventis. A.B.-O. participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MedImmune, Merck/EMD Serono, Novartis, and Sanofi-Genzyme.

Figures

Figure 1.
Figure 1.
Cohort selection. (a) Flow chart of study design and patient disposition. (b) Proportions of patients meeting 2017 McDonald criteria at baseline and in follow-up. Baseline criteria were evaluated on the baseline MRI (acquired within 45 days from clinical onset), in participants with non-ADEM presentation whose MRI scans were performed with administration of gadolinium-based contrast agent. Fulfillment of the McDonald criteria over time was assessed in all participants including at their most recent follow-up; median (IQR) of 8.14 (6.19–9.80) years in MOG-IgG positive participants and of 6.11 (4.06–9.25) years in MOG-IgG negative participants. ADS: acquired demyelinating syndrome; ADEM: acute disseminated encephalomyelitis; AQP-4: aquaporin-4; CSF: cerebrospinal fluid; GAD: gadolinium-based contrast agent enhancement; MOG: myelin oligodendrocyte glycoprotein; MS: multiple sclerosis; NMO: neuromyelitis optica; OCB: oligoclonal band; ON: optic neuritis; TM: transverse myelitis.
Figure 2.
Figure 2.
Baseline clinical and MRI features. Age at clinical presentation (a) and presenting phenotype (b) in MOG-IgG positive and MOG-IgG negative participants. (c)–(h) Brain MRIs of MOG-IgG positive participants demonstrating atypical features: large confluent lesions (c) and (d), extensive pontine lesions (e) and (f), bilateral ill-defined lesions (g) and ill-defined involvement of the temporal cortex (h), and small, non-specific white matter lesions (i) and (j). ADEM: acute disseminated encephalomyelitis; MOG: myelin oligodendrocyte glycoprotein; ON: optic neuritis; TM: transverse myelitis.
Figure 3.
Figure 3.
Clinical and imaging disease course. Each bar indicates the serological follow-up of an individual participant, with dark and light blue colors indicating seropositive and seronegative status, respectively. (a) Colored circles correspond to clinical relapses. Participants initially MOG-IgG positive show a preponderance of episodes of monofocal ON. (b) Black dots indicate the time of acquisition of follow-up brain MRI scans with no new T2 lesions, while the large blue diamonds indicate the follow-up brain MRI with detection of new T2 lesions. New lesions were detected across both seropositive and negative participants, with most MOG-IgG positive participants showing new lesions at the earliest follow-up timepoints, and relatively few subsequently.
Figure 4.
Figure 4.
Summary of features considered atypical for MS. Features considered atypical for MS, in both MOG-IgG positive and MOG-IgG negative participants meeting MS diagnostic criteria. For each serologically defined subgroup, the atypical features are shown at presentation, during the disease course, and at time of their most recent brain MRI scan. As shown in the intersections of the two Venn diagrams, the majority (10/12) of MOG-IgG positive participants exhibited atypical features from initial presentation and throughout their disease course including their most recent MRI, while none (0/53) of the MOG-IgG negative MS patients exhibited any of these atypical features throughout their course. *Minimal lesion load at last MRI evaluation was defined as total T2 lesion volume >0 and <1cc.
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References

    1. Ketelslegers IA, Van Pelt DE, Bryde S, et al.. Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort. Mult Scler 2015; 21(12): 1513–1520. - PubMed
    1. Hacohen Y, Absoud M, Deiva K, et al.. Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol Neuroimmunol Neuroinflamm 2015; 2(2): e81. - PMC - PubMed
    1. Hennes EM, Baumann M, Schanda K, et al.. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 2017; 89: 900–908. - PubMed
    1. Jurynczyk M, Geraldes R, Probert F, et al.. Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis. Brain 2017; 140: 617–627. - PubMed
    1. Hacohen Y, Wong YY, Lechner C, et al.. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol 2018; 75: 478–487. - PMC - PubMed

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