Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults
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.
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.
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.
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.
KeywordsMOG antibodies Titre Prognosis Neuromyelitis optica Optic neuritis Myelitis
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.
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).
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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.