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Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration...

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Autores principales: Taraschenko, Olga, Fox, Howard S., Eldridge, Ember, Wang, Wenyi, Dowd, Samuel W., Al-Saleem, Fetweh, Kattala, Chandana Devi, Dessain, Scott K., Dingledine, Raymond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427020/
https://www.ncbi.nlm.nih.gov/pubmed/34512245
http://dx.doi.org/10.3389/fnins.2021.710650
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author Taraschenko, Olga
Fox, Howard S.
Eldridge, Ember
Wang, Wenyi
Dowd, Samuel W.
Al-Saleem, Fetweh
Kattala, Chandana Devi
Dessain, Scott K.
Dingledine, Raymond
author_facet Taraschenko, Olga
Fox, Howard S.
Eldridge, Ember
Wang, Wenyi
Dowd, Samuel W.
Al-Saleem, Fetweh
Kattala, Chandana Devi
Dessain, Scott K.
Dingledine, Raymond
author_sort Taraschenko, Olga
collection PubMed
description Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified NMDA receptor antibodies from encephalitis patients to mice precipitated seizures, thereby confirming that antibodies are directly pathogenic for seizures. Although different repertoires of anti-NMDA receptor antibodies could contribute to the distinct clinical manifestations in encephalitis patients, the role of specific antibodies in the expression of seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived monoclonal antibodies with distinct epitopes within the N-terminal domain (NTD) of the NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11 antibodies for 2 weeks precipitated seizures, as measured with continuous EEG using cortical screw electrodes. The seizure burden was comparable in all three antibody-treated groups. The seizures were accompanied by increased hippocampal C-C chemokine ligand 2 (CCL2) mRNA expression 3 days after antibody infusion had stopped. Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal antibodies targeting different epitopes within the NMDA receptor may result in a similar seizure phenotype.
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spelling pubmed-84270202021-09-10 Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures Taraschenko, Olga Fox, Howard S. Eldridge, Ember Wang, Wenyi Dowd, Samuel W. Al-Saleem, Fetweh Kattala, Chandana Devi Dessain, Scott K. Dingledine, Raymond Front Neurosci Neuroscience Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis manifests with precipitous cognitive decline, abnormal movements, and severe seizures that can be challenging to control with conventional anti-seizure medications. We previously demonstrated that intracerebroventricular (i.c.v.) administration of cerebrospinal fluid from affected patients, or purified NMDA receptor antibodies from encephalitis patients to mice precipitated seizures, thereby confirming that antibodies are directly pathogenic for seizures. Although different repertoires of anti-NMDA receptor antibodies could contribute to the distinct clinical manifestations in encephalitis patients, the role of specific antibodies in the expression of seizure, motor, and cognitive phenotypes remains unclear. Using three different patient-derived monoclonal antibodies with distinct epitopes within the N-terminal domain (NTD) of the NMDA receptor, we characterized the seizure burden, motor activity and anxiety-related behavior in mice. We found that continuous administration of 5F5, 2G6 or 3C11 antibodies for 2 weeks precipitated seizures, as measured with continuous EEG using cortical screw electrodes. The seizure burden was comparable in all three antibody-treated groups. The seizures were accompanied by increased hippocampal C-C chemokine ligand 2 (CCL2) mRNA expression 3 days after antibody infusion had stopped. Antibodies did not affect the motor performance or anxiety scores in mice. These findings suggest that neuronal antibodies targeting different epitopes within the NMDA receptor may result in a similar seizure phenotype. Frontiers Media S.A. 2021-08-26 /pmc/articles/PMC8427020/ /pubmed/34512245 http://dx.doi.org/10.3389/fnins.2021.710650 Text en Copyright © 2021 Taraschenko, Fox, Eldridge, Wang, Dowd, Al-Saleem, Kattala, Dessain and Dingledine. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Taraschenko, Olga
Fox, Howard S.
Eldridge, Ember
Wang, Wenyi
Dowd, Samuel W.
Al-Saleem, Fetweh
Kattala, Chandana Devi
Dessain, Scott K.
Dingledine, Raymond
Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title_full Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title_fullStr Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title_full_unstemmed Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title_short Monoclonal Antibodies From Anti-NMDA Receptor Encephalitis Patient as a Tool to Study Autoimmune Seizures
title_sort monoclonal antibodies from anti-nmda receptor encephalitis patient as a tool to study autoimmune seizures
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427020/
https://www.ncbi.nlm.nih.gov/pubmed/34512245
http://dx.doi.org/10.3389/fnins.2021.710650
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