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April 2015; 2 (2) ArticleOpen Access

Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children

Yael Hacohen, Michael Absoud, Kumaran Deiva, Cheryl Hemingway, Petra Nytrova, Mark Woodhall, Jacqueline Palace, Evangeline Wassmer, Marc Tardieu, Angela Vincent, Ming Lim, Patrick Waters
First published March 12, 2015, DOI: https://doi.org/10.1212/NXI.0000000000000081
Yael Hacohen
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Michael Absoud
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Kumaran Deiva
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Cheryl Hemingway
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Petra Nytrova
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Mark Woodhall
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Jacqueline Palace
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Evangeline Wassmer
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Marc Tardieu
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Angela Vincent
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Ming Lim
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Patrick Waters
From the Nuffield Department of Clinical Neurosciences (Y.H., M.W., J.P., A.V., M.L., P.W.), John Radcliffe Hospital, University of Oxford, UK; Children's Neurosciences (M.A., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK; Assistance Publique Hôpitaux de Paris (K.D., M.T.), Hopitaux Universitaires Paris Sud, France; Pediatric Neurology Department and National Referral Center for Neuroinflammatory Diseases (K.D., M.T.), Université Paris Sud, Le Kremlin-Bicêtre, Paris, France; Department of Paediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London, UK; Department of Neurology and Center of Clinical Neuroscience (P.N.), General University Hospital in Prague, Czech Republic; First Faculty of Medicine (P.N.), Charles University in Prague, Czech Republic; and Department of Paediatric Neurology (E.W.), Birmingham Children's Hospital, UK.
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Citation
Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children
Yael Hacohen, Michael Absoud, Kumaran Deiva, Cheryl Hemingway, Petra Nytrova, Mark Woodhall, Jacqueline Palace, Evangeline Wassmer, Marc Tardieu, Angela Vincent, Ming Lim, Patrick Waters
Neurol Neuroimmunol Neuroinflamm Apr 2015, 2 (2) e81; DOI: 10.1212/NXI.0000000000000081

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    Figure 1 Full-length MOG cell-based assay using a serum dilution of 1:160 as a cutoff for positivity (red line in both plots)

    (A) Myelin olidgodendrocyte glycoprotein antibodies (MOG-Abs) were detected in a range of childhood demyelination syndromes but not in aquaporin-4 (AQP4)-Ab–positive neuromyelitis optica patients (0/100) or adults with multiple sclerosis (MS) (0/100). There was no correlation between MOG-Ab titer at onset and acquired demyelinating syndrome phenotype (A) or patient age (B). ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; ON = optic neuritis; TM = transverse myelitis.

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    Figure 2 Summary of the utility of MOG-Abs and OCB testing in predicting pediatric disease course at onset compared to clinical follow-up at 1 year

    Following testing with either myelin olidgodendrocyte glycoprotein antibody (MOG-Ab) or oligoclonal blands (OCBs), the additional testing of the respective other is represented by arrows to the respective outcomes. A MOG-Ab–positive test predicted a non–multiple sclerosis (MS) diagnosis, whereas OCB positivity was highly predictive of MS. Eleven of 15 OCB- positive patients developed MS (73%), whereas 11 of 14 OCB-positive and MOG-Abs–negative patients developed MS (79%). The one MOG-Ab–positive and OCB-positive patient did not have MS, and all MOG-Ab–positive and OCB-negative cases had a non-MS course, compared to 91% if only OCB was negative. Of the 14 patients not tested for intrathecal OCBs, 7 patients tested positive for MOG-Ab; 2 patients from the antibody-positive and 2 from the antibody-negative groups had a diagnosis of MS at 1-year follow-up. ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; N/D = not done; ON = optic neuritis; TM = transverse myelitis.

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    Figure 3 Two of 23 MOG-Ab–positive patients were diagnosed with MS compared to 16/42 MOG-Ab–negative patients (p = 0.02, Fisher exact test)

    As myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) were only tested retrospectively, identification of the antibodies did not influence the final diagnosis. One hundred adult patients with multiple sclerosis (MS) and 100 adults with aquaporin-4 (AQP4)-Ab–positive neuromyelitis optica were all MOG-Ab negative. ADEM = acute disseminated encephalomyelitis; CIS = clinically isolated syndrome; ON = optic neuritis; TM = transverse myelitis.

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