ArticleNeurology(R) neuroimmunology & neuroinflammation2021
Placental transfer of NMDAR antibodies causes reversible alterations in mice.
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16 citing papers in PubMed, 42 citations in OpenAlex.
- Nationwide screening identifies an expanded clinical spectrum of anti-KLHL11 antibody-associated neurologic disease in Japan.Journal of neurology · 2026Observational
- Parvalbumin neurons mediate neurological phenotypes of anti-NMDAR encephalitis.Brain : a journal of neurology · 2025Article
- Bridging the gap: insights into sensorimotor deficits in NMDA receptor antibody encephalitis.The Journal of clinical investigation · 2025Article
- Ten Years ofNeurology(R) neuroimmunology & neuroinflammation · 2025Article
- Anti-NMDAR1 antibody impairs dendritic branching in immature cultured neurons.Journal of applied biomedicine · 2024Article
- Impaired functional connectivity of the hippocampus in translational murine models of NMDA-receptor antibody associated neuropsychiatric pathology.Molecular psychiatry · 2024Article
- Purified Serum IgG from a Patient with Anti-IgLON5 Antibody Cause Long-Term Movement Disorders with Impaired Dopaminergic Pathways in Mice.Biomedicines · 2023Article
- Maternal synapsin autoantibodies are associated with neurodevelopmental delay.Frontiers in immunology · 2023Article
- Article
- Myelinating Co-Culture as a Model to Study Anti-NMDAR Neurotoxicity.International journal of molecular sciences · 2022Article
- Anti-IgLON5 antibodies cause progressive behavioral and neuropathological changes in mice.Journal of neuroinflammation · 2022Article
- Impairment of early neuronal maturation in anti-NMDA-receptor encephalitis.Psychopharmacology · 2022Article
- Pregnancy and antibody-mediated CNS disorders: What do we know and what should we know?Frontiers in neurology · 2022Review
- Autoantibodies in neurological disease.Nature reviews. Immunology · 2021Review
- Blocking Placental Class G Immunoglobulin Transfer Prevents NMDA Receptor Antibody Effects in Newborn Mice.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Inhibition of Maternal-to-Fetal Transfer of IgG Antibodies by FcRn Blockade in a Mouse Model of Arthrogryposis Multiplex Congenita.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
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15 authors at 1 institution in 1 country.
Anna García-SerraFrom 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 RadosevicFrom 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 PupakFrom 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 BritoFrom 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 RíosFrom 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 AguilarFrom 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 MaudesFrom 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 AriñoFrom 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 SpatolaFrom 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 MannaraFrom 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 PedreñoFrom 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 JoubertFrom 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 GinésFrom 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 PlanagumàFrom 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 DalmauFrom 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
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer · ES
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo 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.
methodsPregnant 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.
resultsIn 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.
conclusionsIn 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.
Indexed as
Prenatal Exposure Delayed EffectsAnimalsAutoantibodiesBehavior, AnimalBrainFemaleHumansImmunoglobulin GMaternal-Fetal ExchangeMiceMice, Inbred C57BLPlacentaPregnancyPregnancy Complicationsanti-NMDA receptor autoantibodyAutoantibodiesImmunoglobulin G
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