PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Spadaro, M.* ; Winklmeier, S.* ; Beltrán, E.* ; Macrini, C.* ; Höftberger, R.* ; Schuh, E.* ; Thaler, F.S.* ; Gerdes, L.A.* ; Laurent, S.A.* ; Gerhards, R.* ; Brändle, S.* ; Dornmair, K.* ; Breithaupt, C.* ; Krumbholz, M.* ; Moser, M.* ; Kirshnamoorthy, G.* ; Kamp, F.* ; Jenne, D. ; Hohlfeld, R.* ; Kümpfel, T.* ; Lassmann, H.* ; Kawakami, N.* ; Meinl, E.*

Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein.

Ann. Neurol. 84, 315-328 (2018)
Verlagsversion Postprint DOI PMC
Open Access Green
ObjectiveAutoantibodies 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.MethodsPatients 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.ResultsWe 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.InterpretationMOG-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
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
10.244
2.641
73
75
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 Multiple-sclerosis Patients; Nervous-system; Mog-antibody; Myelin/oligodendrocyte Glycoprotein; Autoimmune Encephalomyelitis; Demyelinating Diseases; T-lymphocytes; B-cells; Autoantibodies; Target
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0364-5134
e-ISSN 1531-8249
Zeitschrift Annals of Neurology
Quellenangaben Band: 84, Heft: 2, Seiten: 315-328 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Lung Research
PSP-Element(e) G-501600-001
G-501600-005
DOI 10.1002/ana.25291
WOS ID WOS:000444576400015
PubMed ID 30014603
Erfassungsdatum 2018-07-19
[➜Korrektur melden]