Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis
- A.K. Pröbstel,
- K. Dornmair, PhD,
- R. Bittner,
- P. Sperl,
- D. Jenne, MD,
- S. Magalhaes, MSc,
- A. Villalobos, MSc,
- C. Breithaupt, PhD,
- R. Weissert, MD, PhD,
- U. Jacob, PhD,
- M. Krumbholz, MD,
- T. Kuempfel, MD,
- A. Blaschek, MD,
- W. Stark, MD,
- J. Gärtner, MD,
- D. Pohl, MD, PhD,
- K. Rostasy, MD,
- F. Weber, MD,
- I. Forne, PhD,
- M. Khademi, PhD,
- T. Olsson, MD, PhD,
- F. Brilot, PhD,
- E. Tantsis, MD,
- R.C. Dale, MD, PhD,
- H. Wekerle, MD,
- R. Hohlfeld, MD,
- B. Banwell, MD*,
- A. Bar-Or, MD*,
- E. Meinl, MD* and
- T. Derfuss, MD*
- From the Max Planck Institute of Neurobiology (A.K.P., K.D., R.B., P.S., D.J., M.K., H.W., R.H., E.M., T.D.), Department of Neuroimmunology, Martinsried; Institute of Clinical Neuroimmunology (A.K.P., K.D., R.B., P.S., M.K., T.K., R.H., E.M., T.D.), Department of Pediatric Neurology and Developmental Medicine, Dr von Haunersches Kinderspital (A.B.), and Munich Centre of Integrated Protein Science and Adolf Butenandt Institute (I.F.), Ludwig-Maximilians-University, Munich, Germany; Department of Neurology and Neurosurgery (S.M., A.V., A.B.-O.) and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Canada; Institute of Biochemistry and Biotechnology (C.B.), Martin-Luther-University Halle-Wittenberg, Halle, Germany; Department of Neurology (R.W.), University of Geneva Hospital, Geneva, Switzerland; Westend-Innovation (U.J.), Biotech Consulting, Munich; Department of Pediatrics and Pediatric Neurology (W.S., J.G.), Georg August University, Göttingen, Germany; Children’s Hospital of Eastern Ontario (D.P.), Ottawa, Canada; Division of Neuropediatrics and Inherited Metabolic Disorders (K.R.), Department of Pediatrics, Innsbruck Medical University, Innsbruck, Austria; RG Inflammatory Disorders of the Central Nervous System (F.W.), Max Planck Institute of Psychiatry, Munich, Germany; Neuroimmunology Unit (M.K., T.O.), Department of Clinical Neuroscience, Karolinska University Hospital, Stockholm, Sweden; Neuroimmunology Group (F.B., E.T., R.C.D.), Institute of Neuroscience and Muscle Research, the Kids Research Institute at the Children’s Hospital at Westmead, University of Sydney, Sydney, Australia; Division of Neurology (B.B.), Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada; and Department of Neurology (T.D.), University Hospital Basel, Basel, Switzerland.
- Address correspondence and reprint requests to Prof. Dr. Edgar Meinl, Department of Neuroimmunology, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany meinl{at}neuro.mpg.de
-
↵* These authors contributed equally to this work.
Abstract
Objective: To study the longitudinal dynamics of anti–myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases.
Methods: We addressed the kinetics of anti-MOG immunoglobulins in a prospective study comprising 77 pediatric patients. This was supplemented by a cross-sectional study analyzing 126 pediatric patients with acute demyelination and 62 adult patients with multiple sclerosis (MS). MOG-transfected cells were used for detection of antibodies by flow cytometry.
Results: Twenty-five children who were anti-MOG immunoglobulin (Ig) positive at disease onset were followed for up to 5 years. Anti-MOG antibodies rapidly and continuously declined in all 16 monophasic patients with acute disseminated encephalomyelitis and in one patient with clinically isolated syndrome. In contrast, in 6 of 8 patients (75%) eventually diagnosed with childhood MS, the antibodies to MOG persisted with fluctuations showing a second increase during an observation period of up to 5 years. Antibodies to MOG were mainly IgG 1 and their binding was largely blocked by pathogenic anti-MOG antibodies derived from a spontaneous animal model of autoimmune encephalitis. The cross-sectional part of our study elaborated that anti-MOG Ig was present in about 25% of children with acute demyelination, but in none of the pediatric or adult controls. Sera from 4/62 (6%) adult patients with MS had anti-MOG IgG at low levels.
Conclusions: The persistence or disappearance of antibodies to MOG may have prognostic relevance for acute childhood demyelination.
GLOSSARY
- ADEM=
- acute disseminated encephalomyelitis;
- CIS=
- clinically isolated syndrome;
- HD=
- healthy donor;
- Ig=
- immunoglobulin;
- IgG=
- immunoglobulin G;
- IgM=
- immunoglobulin M;
- mAb=
- monoclonal antibody;
- MCF=
- mean channel fluorescence;
- MOG=
- myelin oligodendrocyte glycoprotein;
- MS=
- multiple sclerosis;
- NTL=
- nontransgenic littermate;
- OND=
- other neurologic disease;
- ONND=
- other non-neurologic disease;
- PE=
- phycoerythrin
Footnotes
-
Study funding: Supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 571), the BMBF (Krankheitsbezogenes Kompetenznetz Multiple Sklerose), Excellence Initiative of the Ludwig-Maximilians-University Munich, the FoeFoLe of the Ludwig-Maximilians-University, the Gemeinnützige Hertie Stiftung, and the Research Foundation of the MS Society of Canada to the Canadian Pediatric Demyelinating Disease Study Group.
-
Supplemental data at www.neurology.org
- Received November 24, 2010.
- Accepted April 6, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
