Maternal neuronal antibodies associated with autism and a language disorder

Dalton, Paola; Deacon, Robert M. J.; Blamire, Andrew M.; Pike, Michael; McKinlay, Ian; Stein, John; Styles, Peter; Vincent, Angela

doi:10.1002/ana.10557

Cited by 191 publications

(157 citation statements)

References 20 publications

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“…Previous studies have also suggested a role for maternal antibodies in the etiology of some cases of autism (Dalton et al, 2003). Moreover, Zimmerman et al (2006) recently reported differing patterns of serum immunoreactivity to pre-natal rat brain between mothers of children with autism and mothers of control children.…”

Section: Discussionmentioning

confidence: 96%

“…However, together with IgG antibodies that are immunoprotective, autoantibodies that react to fetal 'self'-proteins can also cross the placenta. A recent report demonstrated maternal IgG antibody reactivity to rodent Purkinje cells in a mother of multiple children with ASD, as well as the presence of behavioral deficits in pups of a mouse injected during gestation with her serum (Dalton et al, 2003). In another study, mothers of children with autism and their affected children were found to have consistent patterns of antibody reactivity against rat prenatal (day 18) brain proteins.…”

Section: Introductionmentioning

confidence: 91%

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Autism: Maternally derived antibodies specific for fetal brain proteins

et al. 2007

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Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73kDa and 37kDa in plasma from 7 of 61 (11.5%) mothers of children with autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of reactivity to these two bands correlated with a diagnosis of behavioral regression in the child when compared to the TD (p=0.0019) and DD (0.0089) groups. Individual reactivity to the 37kDa band was observed significantly more often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09 -15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with autism, as well as the differential findings between mothers of children with early onset and regressive autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of autism in some children.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 91%

Autism: Maternally derived antibodies specific for fetal brain proteins

et al. 2007

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“…The possibility that some neurodevelopmental diseases were also due to maternal antibodies was proposed and investigated in one case. Serum from a mother of 3 children (1 healthy, 1 with autism, and 1 with a specific language problem) was injected systemically into pregnant mice resulting in motor and behavioral abnormalities in the mouse offspring that persisted into adult life [47]. The role of maternal immune activation and so-far unidentified maternal antibodies in behavioral developmental abnormalities continues to be studied in autism and schizophrenia [48].…”

Section: Antibody-mediated Cns Disordersmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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confidence: 99%

“…Dalton et al (2003) (18) demonstrated maternal IgG antibody reactivity to adult rat cerebellar Purkinje cells in a mother of two children with neurodevelopmental disorders, one with ASD and the other with a severe language disorder. These authors also reported the presence of behavioral deficits in the pups of a mouse injected during gestation with the serum from this woman (18). Similarly, Zimmerman et al (2007) (19) recently reported differing patterns of serum immunoreactivity to prenatal rat brain in specimens from mothers of children already diagnosed with autism compared with specimens from mothers of control children.…”

mentioning

confidence: 99%