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N‐methyl‐D‐aspartate receptor dysfunction by unmutated human antibodies against the NR1 subunit

Anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis related to autoantibody‐mediated synaptic dysfunction. Cerebrospinal fluid–derived human monoclonal NR1 autoantibodies showed low numbers of somatic hypermutations or were unmutated. These unexpected g...

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Detalles Bibliográficos
Autores principales: Wenke, Nina Kerstin, Kreye, Jakob, Andrzejak, Ewa, van Casteren, Adriana, Leubner, Jonas, Murgueitio, Manuela S., Reincke, S. Momsen, Secker, Christopher, Schmidl, Lars, Geis, Christian, Ackermann, Frauke, Nikolaus, Marc, Garner, Craig C., Wardemann, Hedda, Wolber, Gerhard, Prüss, Harald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593665/
https://www.ncbi.nlm.nih.gov/pubmed/30843274
http://dx.doi.org/10.1002/ana.25460
Descripción
Sumario:Anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis related to autoantibody‐mediated synaptic dysfunction. Cerebrospinal fluid–derived human monoclonal NR1 autoantibodies showed low numbers of somatic hypermutations or were unmutated. These unexpected germline‐configured antibodies showed weaker binding to the NMDAR than matured antibodies from the same patient. In primary hippocampal neurons, germline NR1 autoantibodies strongly and specifically reduced total and synaptic NMDAR currents in a dose‐ and time‐dependent manner. The findings suggest that functional NMDAR antibodies are part of the human naïve B cell repertoire. Given their effects on synaptic function, they might contribute to a broad spectrum of neuropsychiatric symptoms. Ann Neurol 2019;85:771–776