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  Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein

Spadaro, M., Winklmeier, S., Beltran, E., Macrini, C., Hoeftberger, R., Schuh, E., et al. (2018). Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Annals of Neurology, 84(2), 315-328. doi:10.1002/ana.25291.

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Spadaro_et_al-2018-Annals_of_Neurology.pdf (Publisher version), 3MB
 
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 Creators:
Spadaro, Melania1, Author
Winklmeier, Stephan1, Author
Beltran, Eduardo1, Author
Macrini, Caterina1, Author
Hoeftberger, Romana1, Author
Schuh, Elisabeth1, Author
Thaler, Franziska S.1, Author
Gerdes, Lisa Ann1, Author
Laurent, Sarah1, Author
Gerhards, Ramona1, Author
Braendle, Simone1, Author
Dornmair, Klaus1, Author
Breithaupt, Constanze1, Author
Krumbholz, Markus1, Author
Moser, Markus2, Author              
Krishnamoorthy, Gurumoorthy3, Author              
Kamp, Frits1, Author
Jenne, Dieter E.4, Author              
Hohlfeld, Reinhard1, Author
Kuempfel, Tania1, Author
Lassmann, Hans1, AuthorKawakami, Naoto1, AuthorMeinl, Edgar1, Author more..
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              
3Krishnamoorthy, Gurumoorthy / Neuroinflammation and Mucosal Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2173635              
4Emeritus Group: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

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Free keywords: MULTIPLE-SCLEROSIS PATIENTS; NERVOUS-SYSTEM; MOG-ANTIBODY; MYELIN/OLIGODENDROCYTE GLYCOPROTEIN; AUTOIMMUNE ENCEPHALOMYELITIS; DEMYELINATING DISEASES; T-LYMPHOCYTES; B-CELLS; AUTOANTIBODIES; TARGETNeurosciences & Neurology;
 Abstract: 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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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000444576400015
DOI: 10.1002/ana.25291
 Degree: -

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Project name : “RELENT”
Grant ID : 668036
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Annals of Neurology
Source Genre: Journal
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Publ. Info: Boston : American Neurological Association
Pages: - Volume / Issue: 84 (2) Sequence Number: - Start / End Page: 315 - 328 Identifier: ISSN: 0364-5134
CoNE: https://pure.mpg.de/cone/journals/resource/954925523748