dc.contributor.author
Peschl, Patrick
dc.contributor.author
Schanda, Kathrin
dc.contributor.author
Zeka, Bleranda
dc.contributor.author
Given, Katherine
dc.contributor.author
Boehm, Denise
dc.contributor.author
Ruprecht, Klemens
dc.contributor.author
Saiz, Albert [u. a.]
dc.date.accessioned
2018-06-08T10:49:34Z
dc.date.available
2017-11-21T10:01:56.338Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21164
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24461
dc.description.abstract
Background Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are
associated with a subset of inflammatory demyelinating diseases of the central
nervous system such as acute disseminated encephalomyelitis and neuromyelitis
optica spectrum disorders. However, whether human MOG antibodies are
pathogenic or an epiphenomenon is still not completely clear. Although MOG is
highly conserved within mammals, previous findings showed that not all human
MOG antibodies bind to rodent MOG. We therefore hypothesized that human MOG
antibody-mediated pathology in animal models may only be evident using
species-specific MOG antibodies. Methods We screened 80 human MOG antibody-
positive samples for their reactivity to mouse and rat MOG using either a live
cell-based assay or immunohistochemistry on murine, rat, and human brain
tissue. Selected samples reactive to either human MOG or rodent MOG were
subsequently tested for their ability to induce complement-mediated damage in
murine organotypic brain slices or enhance demyelination in an experimental
autoimmune encephalitis (EAE) model in Lewis rats. The MOG monoclonal antibody
8-18-C5 was used as a positive control. Results Overall, we found that only a
subset of human MOG antibodies are reactive to mouse (48/80, 60%) or rat
(14/80, 18%) MOG. Purified serum antibodies from 10 human MOG antibody-
positive patients (8/10 reactive to mouse MOG, 6/10 reactive to rat MOG), 3
human MOG-negative patients, and 3 healthy controls were tested on murine
organotypic brain slices. Purified IgG from one patient with high titers of
anti-human, mouse, and rat MOG antibodies and robust binding to myelin tissue
produced significant, complement-mediated myelin loss in organotypic brain
slices, but not in the EAE model. Monoclonal 8-18-C5 MOG antibody caused
complement-mediated demyelination in both the organotypic brain slice model
and in EAE. Conclusion This study shows that a subset of human MOG antibodies
can induce complement-dependent pathogenic effects in a murine ex vivo animal
model. Moreover, a high titer of species-specific MOG antibodies may be
critical for demyelinating effects in mouse and rat animal models. Therefore,
both the reactivity and titer of human MOG antibodies must be considered for
future pathogenicity studies.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Myelin oligodendrocyte glycoprotein
dc.subject
Organotypic slice culture
dc.subject
Neuromyelitis optica spectrum disorders
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Human antibodies against the myelin oligodendrocyte glycoprotein can cause
complement-dependent demyelination
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Journal of Neuroinflammation. - 14 (2017), Artikel Nr. 208
dcterms.bibliographicCitation.doi
10.1186/s12974-017-0984-5
dcterms.bibliographicCitation.url
http://doi.org/10.1186/s12974-017-0984-5
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000028508
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009133
dcterms.accessRights.openaire
open access