TY  - JOUR
AU  - Wenke, Nina Kerstin
AU  - Kreye, Jakob
AU  - Andrzejak, Ewa
AU  - Casteren, Adriana
AU  - Leubner, Jonas
AU  - Murgueitio, Manuela S
AU  - Reincke, S Momsen
AU  - Secker, Christopher
AU  - Schmidl, Lars
AU  - Geis, Christian
AU  - Ackermann, Frauke
AU  - Nikolaus, Marc
AU  - Garner, Craig C
AU  - Wardemann, Hedda
AU  - Wolber, Gerhard
AU  - Prüss, Harald
TI  - N-methyl-D-aspartate receptor dysfunction by unmutated human antibodies against the NR1 subunit.
JO  - Annals of neurology
VL  - 85
IS  - 5
SN  - 0364-5134
CY  - Hoboken, NJ
PB  - Wiley-Blackwell
M1  - DZNE-2020-06991
SP  - 771-776
PY  - 2019
AB  - 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.
KW  - Animals
KW  - Anti-N-Methyl-D-Aspartate Receptor Encephalitis: blood
KW  - Anti-N-Methyl-D-Aspartate Receptor Encephalitis: pathology
KW  - Autoantibodies: blood
KW  - HEK293 Cells
KW  - Hippocampus: chemistry
KW  - Hippocampus: metabolism
KW  - Hippocampus: pathology
KW  - Humans
KW  - Mice
KW  - Neurons: chemistry
KW  - Neurons: metabolism
KW  - Protein Binding: physiology
KW  - Protein Structure, Secondary
KW  - Receptors, N-Methyl-D-Aspartate: blood
KW  - Receptors, N-Methyl-D-Aspartate: chemistry
LB  - PUB:(DE-HGF)16
C6  - pmid:30843274
C2  - pmc:PMC6593665
DO  - DOI:10.1002/ana.25460
UR  - https://pub.dzne.de/record/140669
ER  -