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Gerhards, R.* ; Pfeffer, L.K.* ; Lorenz, J.* ; Starost, L.* ; Nowack, L.* ; Thaler, F.S.* ; Schlüter, M.* ; Rübsamen, H.* ; Macrini, C.* ; Winklmeier, S.* ; Mader, S.* ; Bronge, M.* ; Grönlund, H.* ; Feederle, R. ; Hsia, H.E.* ; Lichtenthaler, S.F.* ; Merl-Pham, J. ; Hauck, S.M. ; Kuhlmann, T.* ; Bauer, I.J.* ; Beltran, E.* ; Gerdes, L.A.* ; Mezydlo, A.* ; Bar-Or, A.* ; Banwell, B.* ; Khademi, M.* ; Olsson, T.* ; Hohlfeld, R.* ; Lassmann, H.* ; Kümpfel, T.* ; Kawakami, N.* ; Meinl, E.*

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

Acta Neuropathol. Commun. 8:207 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autoantigen ; Autoimmunity ; Multiple Sclerosis ; Neuroinflammation; Cd8(+) T-cells; Multiple-sclerosis; Cerebrospinal-fluid; B-cells; Antibodies; Antigens; Receptor; Encephalomyelitis; Autoantibodies; Identification
e-ISSN 2051-5960
Journal Acta Neuropathologica Communications
Quellenangaben Volume: 8, Issue: 1, Pages: , Article Number: 207 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
CF Metabolomics & Proteomics (CF-MPC)
Grants Verein zur Therapieforschung fur MS-Kranke
Werner Reichenberger Stiftung
Projekt DEAL
DFG
Germany's Excellence Strategy