Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice

To determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.Pregnant C57BL/6J mice were administ...

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Autores: García Serra, Anna, Radosevic, Marija, Ríos, José, Aguilar, Esther, Maudes, Estibaliz, Landa Medrano, Jon, Sabater Baudet, Lidia, Martínez Hernández, Eugenia, Planagumà, Jaume, Dalmau Obrador, Josep
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/182706
Acceso en línea:https://hdl.handle.net/2445/182706
Access Level:acceso abierto
Palabra clave:Encefalitis
Autoimmunitat
Immunoglobulines
Encephalitis
Autoimmunity
Immunoglobulins
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spelling Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn MiceGarcía Serra, AnnaRadosevic, MarijaRíos, JoséAguilar, EstherMaudes, EstibalizLanda Medrano, JonSabater Baudet, LidiaMartínez Hernández, EugeniaPlanagumà, JaumeDalmau Obrador, JosepEncefalitisAutoimmunitatImmunoglobulinesEncephalitisAutoimmunityImmunoglobulinsTo determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.Pregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients' or controls' IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls' IgG, patients' IgG, or patients' IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.In pregnant mice that received patients' IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients' IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.FcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients' antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy.2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/182706Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1212/nxi.0000000000001061Neurology-Neuroimmunology & Neuroinflammation, 2021, vol.8, num 6, p. e1061https://doi.org/10.1212/nxi.0000000000001061cc by-nc-nd (c) García Serra, Anna et al., 2021http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1827062026-05-27T06:46:51Z
dc.title.none.fl_str_mv Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
title Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
spellingShingle Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
García Serra, Anna
Encefalitis
Autoimmunitat
Immunoglobulines
Encephalitis
Autoimmunity
Immunoglobulins
title_short Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
title_full Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
title_fullStr Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
title_full_unstemmed Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
title_sort Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice
dc.creator.none.fl_str_mv García Serra, Anna
Radosevic, Marija
Ríos, José
Aguilar, Esther
Maudes, Estibaliz
Landa Medrano, Jon
Sabater Baudet, Lidia
Martínez Hernández, Eugenia
Planagumà, Jaume
Dalmau Obrador, Josep
author García Serra, Anna
author_facet García Serra, Anna
Radosevic, Marija
Ríos, José
Aguilar, Esther
Maudes, Estibaliz
Landa Medrano, Jon
Sabater Baudet, Lidia
Martínez Hernández, Eugenia
Planagumà, Jaume
Dalmau Obrador, Josep
author_role author
author2 Radosevic, Marija
Ríos, José
Aguilar, Esther
Maudes, Estibaliz
Landa Medrano, Jon
Sabater Baudet, Lidia
Martínez Hernández, Eugenia
Planagumà, Jaume
Dalmau Obrador, Josep
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Encefalitis
Autoimmunitat
Immunoglobulines
Encephalitis
Autoimmunity
Immunoglobulins
topic Encefalitis
Autoimmunitat
Immunoglobulines
Encephalitis
Autoimmunity
Immunoglobulins
description To determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.Pregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients' or controls' IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls' IgG, patients' IgG, or patients' IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.In pregnant mice that received patients' IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients' IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.FcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients' antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/182706
url https://hdl.handle.net/2445/182706
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1212/nxi.0000000000001061
Neurology-Neuroimmunology & Neuroinflammation, 2021, vol.8, num 6, p. e1061
https://doi.org/10.1212/nxi.0000000000001061
dc.rights.none.fl_str_mv cc by-nc-nd (c) García Serra, Anna et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) García Serra, Anna et al., 2021
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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