dc.contributor.author
Li, Lucie Y.
dc.contributor.author
Kreye, Jakob
dc.contributor.author
Burek, Malgorzata
dc.contributor.author
Cordero-Gomez, César
dc.contributor.author
Barthel, Paula C.
dc.contributor.author
Sánchez-Sendín, Elisa
dc.contributor.author
Kornau, Hans-Christian
dc.contributor.author
Schmitz, Dietmar
dc.contributor.author
Scharf, Madeleine
dc.contributor.author
Meybohm, Patrick
dc.contributor.author
Reincke, S. Momsen
dc.contributor.author
Prüss, Harald
dc.contributor.author
Höltje, Markus
dc.date.accessioned
2023-09-12T12:57:01Z
dc.date.available
2023-09-12T12:57:01Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40830
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40551
dc.description.abstract
Introduction: The antibody repertoire from CSF-derived antibody-secreting cells and memory B-cells in patients with encephalitis contains a considerable number of antibodies that do not target the disease-defining autoantigen such as the GABA or NMDA receptors. This study focuses on the functional relevance of autoantibodies to brain blood vessels in patients with GABA(A) and NMDA receptor encephalitis.
Methods: We tested 149 human monoclonal IgG antibodies from the cerebrospinal fluid of six patients with different forms of autoimmune encephalitis on murine brain sections for reactivity to blood vessels using immunohistochemistry. Positive candidates were tested for reactivity with purified brain blood vessels, effects on transendothelial electrical resistance (TEER), and expression of tight junction proteins as well as gene regulation using human brain microvascular endothelial hCMEC/D3 cells as in vitro blood-brain barrier model. One blood-vessel reactive antibody was infused intrathecally by pump injection in mice to study in vivo binding and effects on tight junction proteins such as Occludin. Target protein identification was addressed using transfected HEK293 cells.
Results: Six antibodies reacted with brain blood vessels, three were from the same patient with GABA(A)R encephalitis, and the other three were from different patients with NMDAR encephalitis. One antibody from an NMDAR encephalitis patient, mAb 011-138, also reacted with cerebellar Purkinje cells. In this case, treatment of hCMEC/D3 cells resulted in decreased TEER, reduced Occludin expression, and mRNA levels. Functional relevance in vivo was confirmed as Occludin downregulation was observed in mAb 011-138-infused animals. Unconventional Myosin-X was identified as a novel autoimmune target for this antibody.
Discussion: We conclude that autoantibodies to blood vessels occur in autoimmune encephalitis patients and might contribute to a disruption of the blood-brain barrier thereby suggesting a potential pathophysiological relevance of these antibodies.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
blood-brain barrier
en
dc.subject
autoimmunity
en
dc.subject
encephalitis
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Brain blood vessel autoantibodies in patients with NMDA and GABAA receptor encephalitis: identification of unconventional Myosin-X as target antigen
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1077204
dcterms.bibliographicCitation.doi
10.3389/fncel.2023.1077204
dcterms.bibliographicCitation.journaltitle
Frontiers in Cellular Neuroscience
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
17
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
36794262
dcterms.isPartOf.eissn
1662-5102