Alvaro Cobo-Calvo1,2, María Sepúlveda3, Hyacintha d'Indy4, Thais Armangué3,5, Anne Ruiz4, Elisabeth Maillart6, Caroline Papeix6, Bertrand Audoin7, Helene Zephir8, Damien Biotti9, Jonathan Ciron9, Francoise Durand-Dubief10, Nicolas Collongues11, Xavier Ayrignac12, Pierre Labauge12, Eric Thouvenot13, Alexis Montcuquet14, Romain Deschamps15, Nuria Solà-Valls3, Sara Llufriu3, Yolanda Blanco3, Jerome de Seze11, Sandra Vukusic10,16,17, Albert Saiz3, Romain Marignier10,4,17. 1. Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, 59 boulevard Pinel, BRON cedex, 69677, Lyon, France. alvaro.cobo-calvo@chu-lyon.fr. 2. Lyon's Neuroscience Research Center, U1028 INSERM, UMR5292 CNRS, FLUID Team, 69008, Lyon, France. alvaro.cobo-calvo@chu-lyon.fr. 3. Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Center of Neuroimmunology, Neurology Department, Hospital Clínic, Barcelona, Spain. 4. Lyon's Neuroscience Research Center, U1028 INSERM, UMR5292 CNRS, FLUID Team, 69008, Lyon, France. 5. Pediatric Neuroimmunology Unit, Department of Neurology, Sant Joan de Deu Children's Hospital, University of Barcelona, Barcelona, Spain. 6. Department of Neurology, Pitié-Salpêtrière Hospital, APHP, Paris, France. 7. Pôle de Neurosciences Cliniques, Service de Neurologie, Aix Marseille Univ, APHM, Hôpital de La Timone, Marseille, France. 8. Pôle des Neurosciences et de l'Appareil Locomoteur, CHU de Lille, Université de Lille, LIRIC, UMR 995, Lille, France. 9. Department of Neurology B4, Bâtiment Pierre-Paul Riquet, University Hospital of Purpan, Toulouse, France. 10. Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation and Centre de référence pour les maladies inflammatoires rares du cerveau et de la moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, 59 boulevard Pinel, BRON cedex, 69677, Lyon, France. 11. Department of Neurology and Clinical Investigation Center, Strasbourg University Hospital, Strasbourg, France. 12. Multiple Sclerosis Unit, Montpellier University Hospital, Montpellier, France. 13. Department of Neurology, Hôpital Carémeau, Nimes University Hospital, Nimes, France. 14. Department of Neurology, Hôpital de Dupuytren, Limoges, France. 15. Department of Neurology, Fondation A. De Rothschild, Paris, France. 16. Lyon's Neuroscience Research Center, Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, 69003, Lyon, France. 17. Université Claude Bernard Lyon 1, Université de Lyon, 69100, Lyon, France.
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.
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.
Entities:
Keywords:
MOG antibodies; Myelitis; Neuromyelitis optica; Optic neuritis; Prognosis; Titre
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