Significance of Myelin Oligodendrocyte Glycoprotein Antibodies in CSF
A Retrospective Multicenter Study
Abstract
Background and Objectives
Although the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice.
Methods
Eleven medical centers retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF using live cell-based assays. Comparisons were performed using parametric or nonparametric tests, as appropriate. Potential factors of unfavorable outcomes were explored by Cox proportional hazard models and logistic regression.
Results
The cohort included 255 patients: 139 (55%) women and 132 (52%) children (i.e., <18-year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n = 14, 45%) and sensory symptoms (n = 13, 42%), and all but 4 (2 multiple sclerosis, 1 polyradiculoneuritis, and 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher Expanded Disability Status Scale (EDSS) at nadir during the index event (median 4.5, interquartile range [IQR] 3.0–7.5 vs 3.0, IQR 2.0–6.8, p = 0.007) and presented more commonly with sensory (45.5% vs 24%, p = 0.002), motor (33.6% vs 19%, p = 0.021), and sphincter symptoms (26.9% vs 7.8%, p = 0.001) than MOG-Abs seropositive and CSF negative. At the last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p = 0.008). Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at the last follow-up (p ≤ 0.001), and MOG-Abs seronegative and CSF positive status were independently associated with an EDSS ≥3.0.
Discussion
Paired serum and CSF MOG-Abs positivity are common in MOGAD and are associated with a more severe clinical presentation. CSF-only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Reindl M, Schanda K, Woodhall M, et al. International multicenter examination of MOG antibody assays. Neurol Neuroimmunol Neuroinflamm. 2020;7(2):e674.
2.
Jarius S, Paul F, Aktas O, et al. Mog encephalomyelitis: International recommendations on diagnosis and antibody testing. J Neuroinflamm. 2018;15(1):134.
3.
Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019;15(2):89-102.
4.
Cobo-Calvo A, Vukusic S, Marignier R. Clinical spectrum of central nervous system myelin oligodendrocyte glycoprotein autoimmunity in adults. Curr Opin Neurol. 2019;32(3):459-466.
5.
Cobo-Calvo A, Ruiz A, Rollot F, et al. Clinical features and risk of relapse in children and adults with myelin oligodendrocyte glycoprotein antibody–associated disease. Ann Neurol. 2021;89(1):30-41.
6.
Wegener-Panzer A, Cleaveland R, Wendel EM, et al. Clinical and imaging features of children with autoimmune encephalitis and MOG antibodies. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e731.
7.
Armangue T, Olivé-Cirera G, Martínez-Hernandez E, et al. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies : a multicentre observational study. Lancet Neurol. 2020;19(3):234-246.
8.
Waters P, Fadda G, Woodhall M, et al. Serial anti–myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. JAMA Neurol. 2020;77(1):82-93.
9.
Jurynczyk M, Messina S, Woodhall MR, et al. Clinical presentation and prognosis in MOG-antibody disease : a UK study. Brain 2017;140(12):3128-3138.
10.
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(4):478-487.
11.
Brilot F, Dale RC, Selter RC, et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol. 2009;66(6):833-842.
12.
Mariotto S, Ferrari S, Monaco S, et al. Clinical spectrum and IgG subclass analysis of anti - myelin oligodendrocyte glycoprotein antibody - associated syndromes: a multicenter study. J Neurol. 2017;264(12):2420-2430.
13.
Baumann M, Hennes EM, Schanda K, et al. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): extending the spectrum of MOG antibody positive diseases. Mult Scler. 2016;22(14):1821-1829.
14.
Sepúlveda M, Armangue T, Martinez-Hernandez E, et al. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol. 2016;263(7):1349-1360.
15.
Ogawa R, Nakashima I, Takahashi T, et al. MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol Neuroimmunol Neuroinflamm. 2017;4(2):e322.
16.
Cobo-Calvo A, Ruiz A, Maillart E, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology. 2018;90(21):e1858-e1869.
17.
Shor N, Deschamps R, Cobo Calvo A, et al. MRI characteristics of MOG-Ab associated disease in adults: an update. Revue Neurol. 2021;177(1-2):39-50.
18.
Lopez-Chiriboga AS, Sechi E, Buciuc M, et al. Long-term outcomes in patients with myelin oligodendrocyte glycoprotein immunoglobulin G-associated disorder. JAMA Neurol. 2020;77(12):1575-1577.
19.
López-Chiriboga AS, Majed M, Fryer J, et al. Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol. 2018;75(11):1355-1363.
20.
Mayer MC, Meinl E. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more. Ther Adv Neurol Disord. 2012;5(3):147-159.
21.
Spadaro M, Winklmeier S, Beltrán E, et al. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann Neurol. 2018;84(2):315-328.
22.
Tea F, Lopez JA, Ramanathan S, et al. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination. Acta Neuropathol Commun. 2019;7(1):145.
23.
Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflamm. 2016;13(1):279.
24.
Pace S, Orrell M, Woodhall M, et al. Frequency of MOG- IgG in cerebrospinal fluid versus serum. J Neurol Neurosurg Psychiatry. 2021;93(3):334-335.
25.
Mariotto S, Gajofatto A, Batzu L, et al. Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases. Neurology. 2019;93(20):e1867–e1872.
26.
Akaishi T, Takahashi T, Misu T, et al. Difference in the source of anti-AQP4-IgG and anti-MOG-IgG antibodies in CSF in patients with neuromyelitis optica spectrum disorder. Neurology. 2021;97(1):e1-e12.
27.
Kwon YN, Kim B, Kim J-S, et al. Myelin oligodendrocyte glycoprotein-immunoglobulin G in the CSF clinical implication of testing and association with disability. Neurol Neuroimmunol Neuroinflamm. 2022;9(1):e1095.
28.
Carta S, Höftberger R, Bolzan A, et al. Antibodies to MOG in CSF only : pathological findings support the diagnostic value. Acta Neuropathol. 2021;141(5):801-804.
29.
Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173.
30.
Jarius S, Pellkofer H, Siebert N, et al. Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1 : results from 163 lumbar punctures in 100 adult patients. J Neuroinflamm. 2020;17(1):261.
31.
Sabatino JJ, Probstel A-K, Zamvil SS. B cells in autoimmune and neurodegenerative central nervous system diseases. Nat Rev Neurosci. 2019;20(12):728-745.
32.
Kowarik MC, Dzieciatkowska M, Wemlinger S, et al. The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations. J Neuroinflamm. 2015;12:1-8.
33.
Kowarik MC, Astling D, Gasperi C, et al. CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol. 2017;4(6):369-380.
34.
Dalmau J, Gleichman AJ, Hughes EG, et al. Anti-NMDA-receptor encephalitis : case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091-1098.
35.
Malviya M, Barman S, Golombeck KS, et al. NMDAR encephalitis: passive transfer from man to mouse by a recombinant antibody. Ann Clin Transl Neurol. 2017;4(11):768-783.
36.
Bourahoui A, De Seze J, Guttierez R, et al. CSF isoelectrofocusing in a large cohort of MS and other neurological diseases. Eur J Neurol. 2004;11(8):525-529.
37.
Gresa-arribas N, Titulaer MJ, Torrents A, et al. Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis : a retrospective study. Lancet Neurol. 2014;13(2):167-177.
38.
Guasp M, Módena Y, Armangue T, Dalmau J, Graus F. Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis. Neurol Neuroimmunol Neuroinflamm. 2020;7(2):e659.
39.
Carta S, Ferraro D, Ferrari S, Briani C, Mariotto S. Oligoclonal bands: clinical utility and interpretation cues. Crit Rev Clin Lab Sci. 2022;59(6):391-404.
40.
Held F, Kalluri SR, Berthele A, Klein AK, Reindl M, Hemmer B. Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients. Mult Scler J - Exp Transl Clin. 2021;7(2):205521732110227.
41.
Sechi E, Buciuc M, Pittock SJ, et al. Positive predictive value of myelin oligodendrocyte glycoprotein autoantibody testing. JAMA Neurol. 2021;78(6):741-746.
42.
Cruciani C, Puthenparampil M, Tomas-Ojer P, et al. T-cell specificity influences disease heterogeneity in multiple sclerosis. Neurol - Neuroimmunol Neuroinflamm 2021;8(6):e1075.
43.
Joubert B, Saint-Martin M, Noraz N, et al. Characterization of a subtype of autoimmune encephalitis with anti–contactin-associated protein-like 2 antibodies in the cerebrospinal fluid, prominent limbic symptoms, and seizures. JAMA Neurol. 2016;73(9):1115-1124.
44.
Hofman P, Hoyng P, vanderWerf F, Vrensen GF, Schlingemann RO. Lack of blood – brain barrier properties in microvessels of the prelaminar optic nerve head. Invest Ophthalmol Vis Sci. 2001;42(5):895-901.
45.
Killer HE, Jaggi GP, Flammer J, Miller NR, Huber AR, Mironov A. Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional. Brain 2007;130(2):514-520.
46.
Waters PJ, Komorowski L, Woodhall M, et al. A multicenter comparison of MOG-IgG cell-based assays. Neurology 2019;92(11):e1250-e1255.
Letters to the Editor
Information & Authors
Information
Published In
Copyright
© 2022 American Academy of Neurology.
Publication History
Received: March 27, 2022
Accepted: October 24, 2022
Published online: December 16, 2022
Published in issue: March 14, 2023
Disclosure
T. Armangué received speaker honoraria from Biogen, Sanofi-Aventis, and Novartis not related to this manuscript; A. Saiz reports compensation for consulting services and speaker honoraria from Merck-Serono, Biogen-Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd, Novartis, Roche, Alexion, and Janssen; C. Lechner has served as a consultant for Roche but has no conflict of interest with this manuscript; I. Ayzenberg served on scientific advisory boards for Roche, Merck, and Alexion and received research support from Diamed, none related to this article; M. Sepulveda has received speaker honoraria from Biogen and Roche Pharma; E. Martínez-Hernández has received speaker honoraria from Biogen; G. Arrambide has received speaking honoraria and compensation for consulting services or participation in advisory boards from Sanofi, Merck, and Roche; travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS; is editor for Europe of the Multiple Sclerosis Journal – Experimental, Translational, and Clinical; and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. F. Brilot has received research funding from the National Health and Medical Research Council (Australia), Multiple Sclerosis Research Australia, NSW Health, Novartis, and the University of Sydney. She has received speaker honoraria from Novartis, Biogen, Merck, and Limbic Neurology, has been on advisory boards for Merck and Novartis. and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. S. Ramanathan has received research funding from the National Health and Medical Research Council (Australia), the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Neil Hamilton Fairley Early Career Fellowship (APP1141169). She serves as a consultant on an advisory board for UCB and Limbic Neurology, and has been an invited speaker for Biogen, EXCEMED, and Limbic Neurology. S. Ferrari received support for attending scientific meetings by Shire, Sanofi-Genzyme, Roche, and Euroimmun; E. P. Flanagan has served on advisory boards for Alexion, Genentech, and Horizon Therapeutics. He has received speaker honoraria from Pharmacy Times. He received royalties from UpToDate. He was a site primary investigator in a randomized clinical trial on inebilizumab in neuromyelitis optica spectrum disorder run by MedImmune/Viela-Bio/Horizon Therapeutics. He has received funding from the NIH (R01NS113828). He is a member of the medical advisory board of the MOG project. He is an editorial board member of the Journal of the Neurologic Sciences and Neuroimmunology Reports. A patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. M. Reindl is supported by research grants from the Austrian Science Fund (FWF project P32699), the Austrian Research Promotion Agency, Euroimmun, and Roche; consulting fees and advisory board from Roche (to institution) and payments for antibody assays (MOG, AQP4, and other autoantibodies) to institution (University Hospital and Medical University of Innsbruck, Austria). R. Marignier serves on scientific advisory board for Alexion, Horizon Therapeutics, Roche, and UCB; has received honoraria from Alexion, Biogen, Merck, Novartis, and Roche. S. Mariotto received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
Study Funding
This work was supported in part by grants from Plan Nacional de I + D + I and cofinanced by the ISCIII – Subdirección General de Evaluación y Formento de la Investigación Sanitaria and the Fondo Europeo de Desarrollo Regional (ISCIII-FEDER; PI21/00,316 to TA); Fundació Marató de TV3 (37/C/2021, TA and AS), Torrons Vicens Foundation (PFNR0144 to TA); 2021 Invest AEP Grant to TA (PI047351), and 2019 Invest-AEP Support to GO from Pediatric Spanish Society. Instituto de Salud Carlos III, Spain (JR19/00,007, AC-C and JR17/00,012, EM-H). Red Española de Esclerosis múltiple (REEM) (RD16/0015/0002 to Albert Saiz). This work was also supported by a grant from Instituto de Salud Carlos III, Spain; (JR19/00,007 to Álvaro Cobo Calvo).
Authors
Metrics & Citations
Metrics
Citation information is sourced from Crossref Cited-by service.
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Clinical and imaging features and treatment response of anti-NMDAR encephalitis combined with MOGAD, Journal of Clinical Neuroscience, 135, (111114), (2025).https://doi.org/10.1016/j.jocn.2025.111114
- Latin American RAND/UCLA modified Delphi Consensus Recommendations for management and treatment of adult MOGAD patients in clinical practice, Multiple Sclerosis and Related Disorders, (106460), (2025).https://doi.org/10.1016/j.msard.2025.106460
- Oligoclonal bands and kappa free light chains: Competing parameters or complementary biomarkers?, Autoimmunity Reviews, 24, 5, (103765), (2025).https://doi.org/10.1016/j.autrev.2025.103765
- Assessment of neuronal and glial serum biomarkers in myelin oligodendrocyte glycoprotein antibody-associated disease: the MULTIMOGAD study, Journal of Neurology, Neurosurgery & Psychiatry, (jnnp-2024-335137), (2025).https://doi.org/10.1136/jnnp-2024-335137
- Real‐world clinical experience with serum MOG and AQP4 antibody testing by live versus fixed cell‐based assay , Annals of Clinical and Translational Neurology, 12, 3, (556-564), (2025).https://doi.org/10.1002/acn3.52310
- Evaluation of the predictive value of CSF-restricted oligoclonal bands on residual disability and risk of relapse in adult patients with MOGAD: MOGADOC study, Multiple Sclerosis Journal, 31, 3, (290-302), (2025).https://doi.org/10.1177/13524585241311435
- Complement Activation Profiles Predict Clinical Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease, Neurology Neuroimmunology & Neuroinflammation, 12, 1, (2025)./doi/10.1212/NXI.0000000000200340
- Potential mechanisms of how B-cell depletion works in MOGAD, Multiple Sclerosis and Related Disorders, 93, (106269), (2025).https://doi.org/10.1016/j.msard.2025.106269
- MOGAD: A comprehensive review of clinicoradiological features, therapy and outcomes in 4699 patients globally, Autoimmunity Reviews, 24, 1, (103693), (2025).https://doi.org/10.1016/j.autrev.2024.103693
- Frequency of anti-MOG antibodies in serum and CSF of patients with possible autoimmune encephalitis: Results from a Brazilian multicentric study, Multiple Sclerosis and Related Disorders, 92, (106171), (2024).https://doi.org/10.1016/j.msard.2024.106171
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.