Antibodies against fetal brain in sera of mother with autistic children

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States.
Journal of Neuroimmunology (Impact Factor: 2.47). 03/2008; 194(1-2):165-72. DOI: 10.1016/j.jneuroim.2007.11.004
Source: PubMed


Serum antibodies in 100 mothers of children with autistic disorder (MCAD) were compared to 100 age-matched mothers with unaffected children (MUC) using as antigenic substrates human and rodent fetal and adult brain tissues, GFAP, and MBP. MCAD had significantly more individuals with Western immunoblot bands at 36 kDa in human fetal and rodent embryonic brain tissue. The density of bands was greater in fetal brain at 61 kDa. MCAD plus developmental regression had greater reactivity against human fetal brain at 36 and 39 kDa. Data support a possible complex association between genetic/metabolic/environmental factors and the placental transfer of maternal antibodies in autism.

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Available from: Donald C. Gause
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    • "While the etiology of idiopathic ASD is unknown, there are likely numerous distinct etiologies associated with an autism diagnosis given the wide range of behavioral manifestations. A strong association between maternal antibody reactivity toward fetal brain and an outcome of autism in the child has been independently identified by several groups (Dalton et al. 2003; Singer et al. 2008), and a particular pattern of reactivity that is unique to mothers of children with ASD has been identified (Braunschweig et al. 2008; Braunschweig, Duncanson et al. 2012). The same pattern of reactivity has been observed in prospectively collected mid-gestation blood samples from mothers who subsequently gave birth to a child with autism (Croen et al. 2008), supporting the possibility that these antibodies may have a direct effect on neurodevelopment in utero. "
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    ABSTRACT: Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased cellular proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size also and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Full-text · Article · Dec 2014 · Cerebral Cortex
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    • "Maternal brain-reactive antibodies are thought to access the fetal brain during pregnancy as the fetal blood–brain barrier is not yet fully formed. Indeed, studies have identified the presence of antibodies that bind to human fetal brain tissue in a subset of women who have children with autism (Braunschweig et al., 2008; Croen et al., 2008; Singer et al., 2008; Zimmerman et al., 2007). Several studies have described antibodies that are reactive to cerebellar proteins in ASD (Dalton et al., 2003; Goines et al., 2011; Wills et al., 2009). "
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    ABSTRACT: The cerebellum has been long known for its importance in motor learning and coordination. Recently, anatomical, clinical, and neuroimaging studies strongly suggest that the cerebellum supports cognitive functions, including language and executive functions, as well as affective regulation. Furthermore, the cerebellum has emerged as one of the key brain regions affected in autism. Here, we discuss our current understanding of the role of the cerebellum in autism, including evidence from genetic, molecular, clinical, behavioral, and neuroimaging studies. Cerebellar findings in autism suggest developmental differences at multiple levels of neural structure and function, indicating that the cerebellum is an important player in the complex neural underpinnings of autism spectrum disorder, with behavioral implications beyond the motor domain.
    Full-text · Article · Dec 2013 · International Review of Neurobiology
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    • "However, the specific target for autoantibodies that may identify the pathogenic mechanisms involved in the neurobiology of autism has not been identified. Autoantibodies from sera of mothers of children with autism recognize multiple targets in human fetal brain, as demonstrated by immunoblotting [6] [16]. Maternal autoantibodies remain in the baby's circulation for several months until production of own antibodies and memory cells begins. "
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    ABSTRACT: The pathological role of autoantibodies in development of CNS disorders is a new idea with growing interest among neuroscientists. The involvement of autoimmune response in the pathogenesis of autism spectrum disorders (ASD) has been suggested by the presence of multiple brain-specific autoantibodies in children with ASD and in their mothers. The possibility of the effect of autoimmunity on neurogenesis and postnatal brain plasticity has not been determined. The presence of autoantibodies against human neuronal progenitor cells (NPCs) stimulated for neuronal differentiation in culture was tested in sera from children with autism (n=20) and age-matched controls (n=18) by immunoblotting and immunocytochemistry. Immunoreactivity against multiple NPCs proteins of molecular sizes of approximately 55kDa, 105kDa, 150kDa, and 210kDa in sera from individuals with autism had a higher incidence and was stronger than in control sera which immunoreacted mainly with a 150kDa protein. The sera from children with autism immunoreacted the strongest with NPCs expressing neuronal markers Tuj1 and doublecortin, but not astrocyte marker GFAP. The epitopes recognized by antibodies from sera were not human-specific because they detected also NPCs in situ in murine hippocampus. The autoimmune reactions against NPCs suggest an impaired tolerance to neural antigens in autism. These autoantibodies may be symptomatic for autism and furthermore, their presence suggests that autoimmunity may affect postnatal neuronal plasticity particularly after impairment of blood-brain barrier. Future studies will determine the diagnostic value of the presence of autoantibodies in autism and the therapeutic value of prevention of autoimmunity in autism.
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