PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.270
1.331
3
6
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Autoantigen ; Autoimmunity ; Multiple Sclerosis ; Neuroinflammation; Cd8(+) T-cells; Multiple-sclerosis; Cerebrospinal-fluid; B-cells; Antibodies; Antigens; Receptor; Encephalomyelitis; Autoantibodies; Identification
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
e-ISSN 2051-5960
Zeitschrift Acta Neuropathologica Communications
Quellenangaben Band: 8, Heft: 1, Seiten: , Artikelnummer: 207 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30201 - Metabolic Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e) G-502210-001
G-505700-001
Förderungen Verein zur Therapieforschung fur MS-Kranke
Werner Reichenberger Stiftung
Projekt DEAL
DFG
Germany's Excellence Strategy
DOI 10.1186/s40478-020-01086-2
WOS ID WOS:000595819000002
Scopus ID 85096930152
Erfassungsdatum 2020-12-20
[➜Korrektur melden]