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Neurological Review | June 2012

Maternal Autoantibodies in Autism

Daniel Braunschweig, PhD; Judy Van de Water, PhD

Arch Neurol. 2012;69(6):693-699. doi:10.1001/archneurol.2011.2506.

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ABSTRACT

As epidemiologic studies continue to note a striking increase in rates of autism spectrum disorder (ASD) diagnosis around the world, the lack of identified causative agents in most cases remains a major hindrance to the development of treatment and prevention strategies. Published observations of immune system abnormalities in ASD have increased recently, with several groups identifying fetal protein reactive IgG antibodies in plasma from mothers of children with autism. Furthermore, other gestational immune parameters, including maternal infection and dysregulated cytokine signaling, have been found to be associated with ASD in some cases. While detailed pathogenic mechanisms remain to be determined, the hypothesis that some cases of ASD may be influenced, or even caused, by maternal fetal brain–reactive antibodies or other in utero immune-related exposures is an active area of investigation. This article reviews the current literature in this area and proposes several directions for future research.

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Figure. Schematic representation of maternal antibody-associated autism. A, Maternal antibodies that bind to fetal brain proteins may arise through (1) an immune response to a molecular mimic, (2) impaired tolerogenic mechanisms, or (3) alloimmunization to fetal antigens during a previous pregnancy. B, The placenta actively transports maternal IgG into fetal circulation from midgestation through parturition. C, Normally, the adult blood-brain barrier (BBB) excludes circulating IgG from the brain parenchyma, while the developing fetal brain is variably permissive to maternal IgG during gestation. The presence of maternal fetal brain–reactive IgG during critical windows of neurodevelopment appear capable of precipitating adverse offspring behavioral manifestations including autism. CNS indicates central nervous system.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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Braunschweig D, Van de Water J. Maternal Autoantibodies in Autism. Arch Neurol. 2012;69(6):693-699. doi:10.1001/archneurol.2011.2506.

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