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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)
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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
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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
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