Maternal antibodies and developing blood–brain barrier

Kowal, Czeslawa; Andrew, A. Peden; Chen, Huiyi; Diamond, Betty

doi:10.1007/s12026-015-8714-5

Cited by 29 publications

(27 citation statements)

References 58 publications

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“…1 Transfer of maternal antibodies (ABs) in humans starts from gestational week 13 in the second trimester, 2 when the fetal blood-brain barrier (BBB) is still permeable, 3 creating a critical window for potentially harmful antineuronal ABs to compromise fetal brain development. One maternal immune mechanism to protect the fetus is passive immunity, where maternal immunoglobulin G (IgG) is transferred via neonatal Fc receptors (FcRn).…”

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confidence: 99%

“…One maternal immune mechanism to protect the fetus is passive immunity, where maternal immunoglobulin G (IgG) is transferred via neonatal Fc receptors (FcRn). 1 Transfer of maternal antibodies (ABs) in humans starts from gestational week 13 in the second trimester, 2 when the fetal blood-brain barrier (BBB) is still permeable, 3 creating a critical window for potentially harmful antineuronal ABs to compromise fetal brain development. Maternal immune activation including such ABs may therefore influence the etiology of neurodevelopmental disorders, including autism spectrum disorders (ASD), learning disabilities, and schizophrenia.…”

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confidence: 99%

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Human gestational N‐methyl‐d‐aspartate receptor autoantibodies impair neonatal murine brain function

Jurek

Chayka

Kreye

et al. 2019

Annals of Neurology

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Objective: Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N-methyl-D-aspartate receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface ABs, yet little is known about effects on fetal development during pregnancy. Methods: We established a murine model of in utero exposure to human recombinant NR1 and isotype-matched nonreactive control ABs. Pregnant C57BL/6J mice were intraperitoneally injected on embryonic days 13 and 17 each with 240μg of human monoclonal ABs. Offspring were investigated for acute and chronic effects on NMDAR function, brain development, and behavior. Results: Transferred NR1 ABs enriched in the fetus and bound to synaptic structures in the fetal brain. Density of NMDAR was considerably reduced (up to −49.2%) and electrophysiological properties were altered, reflected by decreased amplitudes of spontaneous excitatory postsynaptic currents in young neonates (−34.4%). NR1 AB-treated animals displayed increased early postnatal mortality (+27.2%), impaired neurodevelopmental reflexes, altered blood pH, and reduced bodyweight. During adolescence and adulthood, animals showed hyperactivity (+27.8% median activity over 14 days), lower anxiety, and impaired sensorimotor gating. NR1 ABs caused long-lasting neuropathological effects also in aged mice (10 months), such as reduced volumes of cerebellum, midbrain, and brainstem. Interpretation: The data collectively support a model in which asymptomatic mothers can harbor low-level pathogenic human NR1 ABs that are diaplacentally transferred, causing neurotoxic effects on neonatal development. Thus, ABmediated network changes may represent a potentially treatable neurodevelopmental congenital brain disorder contributing to lifelong neuropsychiatric morbidity in affected children.

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confidence: 99%

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confidence: 99%

Human gestational N‐methyl‐d‐aspartate receptor autoantibodies impair neonatal murine brain function

Jurek

Chayka

Kreye

et al. 2019

Annals of Neurology

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“…IgG1 and IgG4 are most efficiently transferred. Approximately 10% of maternal IgG is thought to pass into the fetal circulation, starting as early as week 13 [60]. The fetal blood brain barrier is not fully developed until the third trimester and may preferentially transfer proteins to the fetal brain [61, 62].…”

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confidence: 99%

Antibody mediated epitope mimicry in the pathogenesis of Zika virus related disease

Homan

Malone²,

Darnell

et al. 2016

Preprint

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“…And at last, how do these antibodies gain access to and persist in naive neural tissue? Recent studies show that maternal antibodies can transfer into the developing peripheral and central nervous system during gestation [11,18]. These findings coupled with reports that maternal antibodies are effective against congenital Zika [19] and cytomegalovirus [20] infections suggest a broader applicability of maternal immunizations to other TORCH pathogens.…”

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confidence: 89%