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Published in: Journal of Neurology 4/2019

01-04-2019 | Optic Neuritis | Original Communication

Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults

Authors: Alvaro Cobo-Calvo, María Sepúlveda, Hyacintha d’Indy, Thais Armangué, 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, Nuria Solà-Valls, Sara Llufriu, Yolanda Blanco, Jerome de Seze, Sandra Vukusic, Albert Saiz, Romain Marignier, The OFSEP Group, The REEM Group

Published in: Journal of Neurology | Issue 4/2019

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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.
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Literature
1.
go back to reference Sato DK, Callegaro D, Lana-Peixoto MA et al (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82:474–481CrossRefPubMedPubMedCentral Sato DK, Callegaro D, Lana-Peixoto MA et al (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82:474–481CrossRefPubMedPubMedCentral
2.
go back to reference 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 21:866–874CrossRefPubMed 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 21:866–874CrossRefPubMed
3.
go back to reference Jurynczyk M, Messina S, Woodhall MR et al (2017) Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 140:3128–3138CrossRefPubMed Jurynczyk M, Messina S, Woodhall MR et al (2017) Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 140:3128–3138CrossRefPubMed
4.
go back to reference 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–e1869CrossRefPubMed 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–e1869CrossRefPubMed
5.
go back to reference Hennes E-M, Baumann M, Schanda K et al (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908CrossRefPubMed Hennes E-M, Baumann M, Schanda K et al (2017) Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89:900–908CrossRefPubMed
6.
go back to reference 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 86:265–272CrossRefPubMed 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 86:265–272CrossRefPubMed
7.
go back to reference Cobo-Calvo Á, Ruiz A, D’Indy H et al (2017) MOG antibody-related disorders: common features and uncommon presentations. J Neurol 264:1945–1955CrossRefPubMed Cobo-Calvo Á, Ruiz A, D’Indy H et al (2017) MOG antibody-related disorders: common features and uncommon presentations. J Neurol 264:1945–1955CrossRefPubMed
8.
go back to reference 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 13:279CrossRefPubMedPubMedCentral 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 13:279CrossRefPubMedPubMedCentral
9.
go back to reference 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 88:811–817CrossRefPubMed 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 88:811–817CrossRefPubMed
10.
go back to reference 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 75:1355–1363CrossRefPubMedPubMedCentral 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 75:1355–1363CrossRefPubMedPubMedCentral
11.
go back to reference Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189CrossRefPubMedPubMedCentral Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189CrossRefPubMedPubMedCentral
12.
go back to reference Huppke P, Rostasy K, Karenfort M et al (2013) Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 19:941–946CrossRefPubMed Huppke P, Rostasy K, Karenfort M et al (2013) Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 19:941–946CrossRefPubMed
13.
go back to reference Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentral Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302CrossRefPubMedPubMedCentral
14.
go back to reference 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 22:312–319CrossRefPubMed 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 22:312–319CrossRefPubMed
15.
go back to reference Marignier R, Bernard-Valnet R, Giraudon P et al (2013) Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 80:2194–2200CrossRefPubMed Marignier R, Bernard-Valnet R, Giraudon P et al (2013) Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 80:2194–2200CrossRefPubMed
16.
go back to reference 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 263:1349–1360CrossRefPubMedPubMedCentral 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 263:1349–1360CrossRefPubMedPubMedCentral
17.
go back to reference Kaneko K, Sato DK, Nakashima I et al (2016) Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J Neurol Neurosurg Psychiatry 87:1257–1259CrossRefPubMed Kaneko K, Sato DK, Nakashima I et al (2016) Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J Neurol Neurosurg Psychiatry 87:1257–1259CrossRefPubMed
18.
go back to reference 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 89:927–936CrossRefPubMedPubMedCentral 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 89:927–936CrossRefPubMedPubMedCentral
19.
go back to reference 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 14:1–6CrossRefPubMed 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 14:1–6CrossRefPubMed
20.
go back to reference Miller DJ, Duka T, Stimpson CD et al (2012) Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci 109:16480–16485CrossRefPubMed Miller DJ, Duka T, Stimpson CD et al (2012) Prolonged myelination in human neocortical evolution. Proc Natl Acad Sci 109:16480–16485CrossRefPubMed
21.
go back to reference Fernandez-Carbonell C, Vargas-Lowy D, Musallam A et al (2016) Clinical and MRI phenotype of children with MOG antibodies. Mult Scler 22:174–184CrossRefPubMed Fernandez-Carbonell C, Vargas-Lowy D, Musallam A et al (2016) Clinical and MRI phenotype of children with MOG antibodies. Mult Scler 22:174–184CrossRefPubMed
22.
go back to reference McKeon A, Lennon VA, Lotze T et al (2008) CNS aquaporin-4 autoimmunity in children. Neurology 71:93–100CrossRefPubMed McKeon A, Lennon VA, Lotze T et al (2008) CNS aquaporin-4 autoimmunity in children. Neurology 71:93–100CrossRefPubMed
23.
go back to reference 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 67:195–205CrossRefPubMed 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 67:195–205CrossRefPubMed
24.
go back to reference Verheul MK, Fearon U, Trouw LA, Veale DJ (2015) Biomarkers for rheumatoid and psoriatic arthritis. Clin Immunol 161:2–10CrossRefPubMed Verheul MK, Fearon U, Trouw LA, Veale DJ (2015) Biomarkers for rheumatoid and psoriatic arthritis. Clin Immunol 161:2–10CrossRefPubMed
25.
go back to reference Tremlett H, Zhao Y, Joseph J et al (2008) Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 79:1368–1374CrossRefPubMed Tremlett H, Zhao Y, Joseph J et al (2008) Relapses in multiple sclerosis are age- and time-dependent. J Neurol Neurosurg Psychiatry 79:1368–1374CrossRefPubMed
26.
go back to reference 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 135:1834–1849CrossRefPubMed 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 135:1834–1849CrossRefPubMed
27.
go back to reference 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:e89CrossRef 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:e89CrossRef
28.
go back to reference Peschl P, Schanda K, Zeka B et al (2017) Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination. J Neuroinflammation 14:208CrossRefPubMedPubMedCentral Peschl P, Schanda K, Zeka B et al (2017) Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination. J Neuroinflammation 14:208CrossRefPubMedPubMedCentral
29.
go back to reference 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 141:1063–1074CrossRefPubMedPubMedCentral 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 141:1063–1074CrossRefPubMedPubMedCentral
30.
go back to reference Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: International recommendations on diagnosis and antibody testing. J Neuroinflammation 15:134CrossRefPubMedPubMedCentral Jarius S, Paul F, Aktas O et al (2018) MOG encephalomyelitis: International recommendations on diagnosis and antibody testing. J Neuroinflammation 15:134CrossRefPubMedPubMedCentral
Metadata
Title
Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults
Authors
Alvaro Cobo-Calvo
María Sepúlveda
Hyacintha d’Indy
Thais Armangué
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
Nuria Solà-Valls
Sara Llufriu
Yolanda Blanco
Jerome de Seze
Sandra Vukusic
Albert Saiz
Romain Marignier
The OFSEP Group
The REEM Group
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 4/2019
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-018-9160-9

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