Placental transfer of NMDAR antibodies causes reversible alterations in mice.

Animals Autoantibodies / toxicity Behavior, Animal Brain / pathology Female Humans Immunoglobulin G Maternal-Fetal Exchange Mice Mice, Inbred C57BL Placenta Pregnancy Pregnancy Complications Prenatal Exposure Delayed Effects

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
01 2021
Historique:
received: 13 07 2020
accepted: 26 08 2020
entrez: 11 11 2020
pubmed: 12 11 2020
medline: 13 10 2021
Statut: epublish

Résumé

To determine whether maternofetal transfer of NMDA receptor (NMDAR) antibodies has pathogenic effects on the fetus and offspring, we developed a model of placental transfer of antibodies. Pregnant C57BL/6J mice were administered via tail vein patients' or controls' immunoglobulin G (IgG) on days 14-16 of gestation, when the placenta is able to transport IgG and the immature fetal blood-brain barrier is less restrictive to IgG crossing. Immunohistochemical and DiOlistic (gene gun delivery of fluorescent dye) staining, confocal microscopy, standardized developmental and behavioral tasks, and hippocampal long-term potentiation were used to determine the antibody effects. In brains of fetuses, patients' IgG, but not controls' IgG, bound to NMDAR, causing a decrease in NMDAR clusters and cortical plate thickness. No increase in neonatal mortality was observed, but offspring exposed in utero to patients' IgG had reduced levels of cell-surface and synaptic NMDAR, increased dendritic arborization, decreased density of mature (mushroom-shaped) spines, microglial activation, and thinning of brain cortical layers II-IV with cellular compaction. These animals also had a delay in innate reflexes and eye opening and during follow-up showed depressive-like behavior, deficits in nest building, poor motor coordination, and impaired social-spatial memory and hippocampal plasticity. Remarkably, all these paradigms progressively improved (becoming similar to those of controls) during follow-up until adulthood. In this model, placental transfer of patients' NMDAR antibodies caused severe but reversible synaptic and neurodevelopmental alterations. Reversible antibody effects may contribute to the infrequent and limited number of complications described in children of patients who develop anti-NMDAR encephalitis during pregnancy.

Identifiants

DOI: 10.1212/NXI.0000000000000915 PMID: 33172961 PMC: PMC7713722
pubmed: 33172961
pii: 8/1/e915
doi: 10.1212/NXI.0000000000000915
pmc: PMC7713722
pii:
doi:

Substances chimiques

Autoantibodies 0
Immunoglobulin G 0
anti-NMDA receptor autoantibody 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Anna García-Serra (A)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.
ORCID: 0000-0002-9609-2290

Marija Radosevic (M)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Anika Pupak (A)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Veronica Brito (V)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

José Ríos (J)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Esther Aguilar (E)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Estibaliz Maudes (E)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Helena Ariño (H)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Marianna Spatola (M)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.
ORCID: 0000-0003-2548-0429

Francesco Mannara (F)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Marta Pedreño (M)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Bastien Joubert (B)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Silvia Ginés (S)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Jesús Planagumà (J)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain.

Josep Dalmau (J)

From the Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (A.G.-S., M.R., A.P., V.B., E.A., E.M., H.A., M.S., F.M., M.P., B.J., S.G., J.P., J.D.), Hospital Clínic, Universitat de Barcelona; Departament de Biomedicina (A.P., V.B., S.G.), Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) (A.P., V.B., S.G.), Madrid; Medical Statistics Core Facility (J.R.), IDIBAPS and Hospital Clínic, Barcelona; Biostatistics Unit (J.R.), School of Medicine, Universitat Autònoma de Barcelona; Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER) (J.D.), Madrid, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (ICREA) (J.D.), Barcelona, Spain. jdalmau@clinic.cat.
ORCID: 0000-0001-5856-2813

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Autoanticorps › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Échange foetomaternel › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Structures de l'embryon › Placenta › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Grossesse › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Maladies urogénitales › Maladies de l'appareil urogénital féminin et complications de la grossesse › Complications de la grossesse › Placental transfer of NMDAR antibodies causes...
questionsmedicales.fr › Maladies urogénitales › Maladies de l'appareil urogénital féminin et complications de la grossesse › Complications de la grossesse › Lésions prénatales › Effets différés de l'exposition prénatale à des facteurs de risque › Placental transfer of NMDAR antibodies causes...