Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein
Melania Spadaro PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorStephan Winklmeier MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorEduardo Beltrán PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorCaterina Macrini MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorRomana Höftberger MD
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorElisabeth Schuh MD, PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorFranziska S. Thaler MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorLisa Ann Gerdes MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorSarah Laurent MD, PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorRamona Gerhards MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorSimone Brändle PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorKlaus Dornmair PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorConstanze Breithaupt PhD
Department of Physical Biotechnology, Martin Luther University of Halle-Wittenberg, Halle, Germany
Search for more papers by this authorMarkus Krumbholz MD
Department of Neurology and Hertie Institute for Clinical Brain Research, Eberhard Karl University, Tübingen, Germany
Search for more papers by this authorMarkus Moser PhD
Max Planck Institute of Biochemistry, Martinsried, Germany
Search for more papers by this authorGurumoorthy Krishnamoorthy PhD
Max Planck Institute of Biochemistry, Martinsried, Germany
Search for more papers by this authorFrits Kamp PhD
Department of Biophysics, Biomedical Center, Ludwig Maximilian University of Munich, Munich, Germany
Search for more papers by this authorDieter Jenne MD
Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, and Max Planck Institute of Neurobiology, Planegg-Martinsried, Germany
Search for more papers by this authorReinhard Hohlfeld MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Munich Cluster for Systems Neurology, Munich, Germany
Search for more papers by this authorTania Kümpfel MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorHans Lassmann MD
Center for Brain Research, Medical University of Vienna, Austria
Search for more papers by this authorNaoto Kawakami PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Naoto Kawakami and Edgar Meinl contributed equally
Search for more papers by this authorCorresponding Author
Edgar Meinl MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Naoto Kawakami and Edgar Meinl contributed equally
Address correspondence to: Dr Meinl, Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str 9, 82152 Planegg-Martinsried, Germany. E-mail: [email protected]Search for more papers by this authorMelania Spadaro PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorStephan Winklmeier MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorEduardo Beltrán PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorCaterina Macrini MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorRomana Höftberger MD
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorElisabeth Schuh MD, PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorFranziska S. Thaler MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorLisa Ann Gerdes MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorSarah Laurent MD, PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorRamona Gerhards MSc
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorSimone Brändle PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorKlaus Dornmair PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorConstanze Breithaupt PhD
Department of Physical Biotechnology, Martin Luther University of Halle-Wittenberg, Halle, Germany
Search for more papers by this authorMarkus Krumbholz MD
Department of Neurology and Hertie Institute for Clinical Brain Research, Eberhard Karl University, Tübingen, Germany
Search for more papers by this authorMarkus Moser PhD
Max Planck Institute of Biochemistry, Martinsried, Germany
Search for more papers by this authorGurumoorthy Krishnamoorthy PhD
Max Planck Institute of Biochemistry, Martinsried, Germany
Search for more papers by this authorFrits Kamp PhD
Department of Biophysics, Biomedical Center, Ludwig Maximilian University of Munich, Munich, Germany
Search for more papers by this authorDieter Jenne MD
Comprehensive Pneumology Center (CPC), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Munich, and Max Planck Institute of Neurobiology, Planegg-Martinsried, Germany
Search for more papers by this authorReinhard Hohlfeld MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Munich Cluster for Systems Neurology, Munich, Germany
Search for more papers by this authorTania Kümpfel MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Search for more papers by this authorHans Lassmann MD
Center for Brain Research, Medical University of Vienna, Austria
Search for more papers by this authorNaoto Kawakami PhD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Naoto Kawakami and Edgar Meinl contributed equally
Search for more papers by this authorCorresponding Author
Edgar Meinl MD
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Munich, Germany
Naoto Kawakami and Edgar Meinl contributed equally
Address correspondence to: Dr Meinl, Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str 9, 82152 Planegg-Martinsried, Germany. E-mail: [email protected]Search for more papers by this authorAbstract
Objective
Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with inflammatory demyelinating diseases of the central nervous system (CNS). We analyzed their pathogenic activity by affinity-purifying these antibodies (Abs) from patients and transferring them to experimental animals.
Methods
Patients with Abs to MOG were identified by cell-based assay. We determined the cross-reactivity to rodent MOG and the recognized MOG epitopes. We produced the correctly folded extracellular domain of MOG and affinity-purified MOG-specific Abs from the blood of patients. These purified Abs were used to stain CNS tissue and transferred in 2 models of experimental autoimmune encephalomyelitis. Animals were analyzed histopathologically.
Results
We identified 17 patients with MOG Abs from our outpatient clinic and selected 2 with a cross-reactivity to rodent MOG; both had recurrent optic neuritis. Affinity-purified Abs recognized MOG on transfected cells and stained myelin in tissue sections. The Abs from the 2 patients recognized different epitopes on MOG, the CC′ and the FG loop. In both patients, these Abs persisted during our observation period of 2 to 3 years. The anti-MOG Abs from both patients were pathogenic upon intrathecal injection in 2 different rat models. Together with cognate MOG-specific T cells, these Abs enhanced T-cell infiltration; together with myelin basic protein–specific T cells, they induced demyelination associated with deposition of C9neo, resembling a multiple sclerosis type II pathology.
Interpretation
MOG-specific Abs affinity purified from patients with inflammatory demyelinating disease induce pathological changes in vivo upon cotransfer with myelin-reactive T cells, suggesting that these Abs are similarly pathogenic in patients. Ann Neurol 2018;84:315–328
Potential Conflicts of Interest
Nothing to report.
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