Abstract
Objective
To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions.
Methods
This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI.
Results
MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype.
Conclusion
High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Change history
07 February 2019
The original version of this article unfortunately contained a mistake.
References
Sato DK, Callegaro D, Lana-Peixoto MA et al (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82:474–481
Höftberger R, Sepulveda M, Armangue T et al (2015) Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler 21:866–874
Jurynczyk M, Messina S, Woodhall MR et al (2017) Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 140:3128–3138
Cobo-Calvo A, Ruiz A, Maillart E et al (2018) Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology 90:e1858–e1869
Hennes E-M, Baumann M, Schanda K et al (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908
Baumann M, Sahin K, Lechner C et al (2015) Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry 86:265–272
Cobo-Calvo Á, Ruiz A, D’Indy H et al (2017) MOG antibody-related disorders: common features and uncommon presentations. J Neurol 264:1945–1955
Jarius S, Ruprecht K, Kleiter I et al (2016) 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 Neuroinflammation 13:279
Hyun J-W, Woodhall MR, Kim S-H et al (2017) Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry 88:811–817
López-Chiriboga AS, Majed M, Fryer J et al (2018) Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol 75:1355–1363
Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189
Huppke P, Rostasy K, Karenfort M et al (2013) Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 19:941–946
Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302
Cobo-Calvo Á, Sepúlveda M, Bernard-Valnet R et al (2016) Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: clinical and prognostic implications. Mult Scler 22:312–319
Marignier R, Bernard-Valnet R, Giraudon P et al (2013) Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 80:2194–2200
Sepúlveda M, Armangue T, Martinez-Hernandez E et al (2016) Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol 263:1349–1360
Kaneko K, Sato DK, Nakashima I et al (2016) Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J Neurol Neurosurg Psychiatry 87:1257–1259
Kaneko K, Sato DK, Nakashima I et al (2018) CSF cytokine profile in MOG-IgG + neurological disease is similar to AQP4-IgG + NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry 89:927–936
Hasegawa M, Houdou S, Mito T et al (1992) Development of myelination in the human fetal and infant cerebrum: a myelin basic protein immunohistochemical study. Brain Dev 14:1–6
Miller DJ, Duka T, Stimpson CD et al (2012) Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci 109:16480–16485
Fernandez-Carbonell C, Vargas-Lowy D, Musallam A et al (2016) Clinical and MRI phenotype of children with MOG antibodies. Mult Scler 22:174–184
McKeon A, Lennon VA, Lotze T et al (2008) CNS aquaporin-4 autoimmunity in children. Neurology 71:93–100
Bertsias G, Ioannidis J, Boletis J et al (2008) EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 67:195–205
Verheul MK, Fearon U, Trouw LA, Veale DJ (2015) Biomarkers for rheumatoid and psoriatic arthritis. Clin Immunol 161:2–10
Tremlett H, Zhao Y, Joseph J et al (2008) Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 79:1368–1374
Kitley J, Leite MI, Nakashima I et al (2012) Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain 135:1834–1849
Waters P, Woodhall M, O’Connor KC et al (2015) MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol NeuroInflammation 2:e89
Peschl P, Schanda K, Zeka B et al (2017) Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination. J Neuroinflammation 14:208
Wilson R, Makuch M, Kienzler A-K et al (2018) Condition-dependent generation of aquaporin-4 antibodies from circulating B cells in neuromyelitis optica. Brain 141:1063–1074
Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: International recommendations on diagnosis and antibody testing. J Neuroinflammation 15:134
Acknowledgements
The authors thank the group of NeuroBioTec from Hospices Civils de Lyon for supporting this study. Members of the OFSEP group: Alvaro Cobo- Calvo, Hyacintha d'Indy, Anne Ruiz, Elisabeth Maillart, Caroline Papeix, Bertrand Audoin, Helene Zephir, Damien Biotti, Jonathan Ciron, Francoise Durand-Dubief, Nicolas Collongues, Xavier Ayrignac, Pierre Labauge, Eric Thouvenot, Alexis Montcuquet, Romain Deschamps, Jerome de Seze, Sandra Vukusic, Romain Marignier. Members of the REEM group: María Sepúlveda, Thais Armangué, Nuria Solà- Valls, Sara Llufriu, Yolanda Blanco, Albert Saiz.
Funding
The present study is supported by a grant from ARSEP foundation and a grant provided by the French State and handled by the “Agence Nationale de la Recherche”, within the framework of the “Investments for the Future” programme, under the reference ANR-10-COHO-002 Observatoire Français de la Sclérose en Plaques (OFSEP), by the Eugene Devic Foundation against Multiple Sclerosis (EDMUS Foundation), by Red Española de Esclerosis Múltiple (REEM), Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER, “Otra manera de hacer Europa”) (RD16/0015/0002); and by Fundació Marató de TV3 (20141830).
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Conflicts of interest
Cobo-Calvo, Sepulveda, d’Indy, Armangué and Ruiz report no disclosures. Maillart has received consulting and lecturing fees, and travel grants from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma, and research support from Novartis and Roche. Audoin reports no disclosures. Zephir reports no disclosures. Jonathan Ciron serves on scientific advisory board for Merck Serono and Roche, and has received funding for travel and honoraria from Biogen, Novartis, Genzyme, Teva Pharmaceuticals, Merck Serono and Roche, with no relation with the submitted work. Ayrignac and Thouvenot report no disclosures. Montcuquet has received funding for travel from Merck Serono, Teva, Novartis, Sanofi-Genzyme and Biogen. Solà Valls received consulting and travel grants from Biogen Idec, Genzyme-Sanofi, Merck Serono, and Bayer-Schering. Llufriu reports no disclosures. Papeix reports no disclosures. Biotti has received consulting and lecturing fees, and travel grants from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma. Durand-Dubief serves on scientific advisory board for Merck Serono and has received funding for travel and honoraria from Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Roche and Teva. Collongues has received honoraria for consulting or presentation from Biogen Idec, Almirall, Novartis, Merck Serono, LFB, Teva Pharma, Sanofi-Genzyme, Roche, and is a member of the editorial board of the Journal de la Ligue Française contre la Sclérose en plaques, with no relation with the submitted work. Labauge reports no disclosure. Deschamps has received travels grants from Biogen Idec. De Seze reports no disclosures. Vukusic has received consulting and lecturing fees, travel grants and research support from Biogen, Geneuro, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharm. Blanco reports no disclosures. Saiz has received travel funding and/or speaker honoraria from Bayer-Schering, Merck-Serono, Biogen Idec, Sanofi-Aventis, Teva Pharmaceutical Industries, Novartis and Roche. Marignier has received consulting and lecturing fees, travel grants and research support from Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.
Additional information
The original version of this article was revised: There is a mistake in the surname of the third author. She is Hyacintha d’Indy and not Hyacintha ’Indy.
Electronic supplementary material
Below is the link to the electronic supplementary material.
415_2018_9160_MOESM1_ESM.tif
Supplementary Figure 1. MOG mean fluorescence intensity from different determinations. (a) non-transfected HEK293 cells, (b) transfected HEK293cells with MOG and green fluorescence protein (GFP), (c) serum from negative control, (d) serum from positive control, (e) MOG-ratio ΔMFI from one MOG-Ab- positive patient (TIF 199 KB)
415_2018_9160_MOESM2_ESM.tif
Supplementary Figure 2. Distribution of clinical phenotype regarding MOG-Ab titres (a) MOG-Ab titres at onset and, (b) at last follow-up (TIF 114 KB)
Rights and permissions
About this article
Cite this article
Cobo-Calvo, A., Sepúlveda, M., d’Indy, H. et al. Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults. J Neurol 266, 806–815 (2019). https://doi.org/10.1007/s00415-018-9160-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-018-9160-9