Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS.

Autor: Gerhards R; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Pfeffer LK; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Lorenz J; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Starost L; Institute of Neuropathology, University Hospital Münster, Münster, Germany., Nowack L; Institute of Neuropathology, University Hospital Münster, Münster, Germany., Thaler FS; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Schlüter M; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Rübsamen H; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Macrini C; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Winklmeier S; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Mader S; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Bronge M; Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Grönlund H; Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Feederle R; Institute for Diabetes and Obesity, Monoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Neuherberg, Germany., Hsia HE; Neuroproteomics, School of Medicine, Klinikum rechts der Isar, German Center for Neurodegenerative Diseases (DZNE), Technical University of Munich, Munich, Germany., Lichtenthaler SF; Neuroproteomics, School of Medicine, Klinikum rechts der Isar, German Center for Neurodegenerative Diseases (DZNE), Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Merl-Pham J; Research Unit Protein Science, Helmholtz Center Munich, Munich, Germany., Hauck SM; Research Unit Protein Science, Helmholtz Center Munich, Munich, Germany., Kuhlmann T; Institute of Neuropathology, University Hospital Münster, Münster, Germany., Bauer IJ; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Beltran E; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Gerdes LA; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Mezydlo A; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Bar-Or A; Department of Neurology, University of Pennsylvania, Philadelphia, USA., Banwell B; Children's Hospital of Philadelphia, Philadelphia, USA., Khademi M; Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Olsson T; Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Hohlfeld R; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Lassmann H; Center for Brain Research, Medical University, Vienna, Austria., Kümpfel T; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Kawakami N; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany., Meinl E; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152, Planegg-Martinsried, Germany. edgar.meinl@med.uni-muenchen.de.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2020 Nov 30; Vol. 8 (1), pp. 207. Date of Electronic Publication: 2020 Nov 30.
DOI: 10.1186/s40478-020-01086-2
Abstrakt: Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.
Databáze: MEDLINE
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