Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder
Open accessAbstract
Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement.
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Nordahl et al. found that children born to mothers with this autoantibody binding pattern had higher total cerebral volume than ASD children born to autoantibody-negative mothers and typically developing controls.
“children born to mothers with this pattern of autoantibody binding also exhibited higher total cerebral volume when compared both to children with ASD born to autoantibody-negative mothers as well as typically developing control children”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Nordahl et al, 2013
In a rhesus monkey model of maternal autoantibody exposure, brain volume is increased, as has been described in children with autism born to mothers with the autoantibodies.
“In a similar model generated in rhesus monkeys, brain volume is increased [24], as has been described in children with autism born to mothers with the autoantibodies [259].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [259]
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- Braunschweig D Duncanson P Boyce R Hansen R Ashwood P Pessah IN Hertz-Picciotto I Van de Water J 2012 Behavioral correlates of maternal antibody status among children with autism J Autism Dev Disord 42 1435 1445 22012245 PMC4871696
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- Authors
- Nordahl, C. W., Braunschweig, D., Iosif, A.-M., Lee, A., Rogers, S., Ashwood, P., Amaral, D. G., & Van de Water, J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Nordahl, Christine Wu
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 30
- Pages
- 61-65
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3641177
- OpenAlex
- W2020042000
- Cited by
- 95
- References
- 28
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 11 · 2018: 13 · 2017: 5 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 5
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P51OD011107)
- National Institute of Mental Health (U24MH081810, R00MH085099, T32MH073124, R01MH089626)
- National Institute of Environmental Health Sciences (P01ES011269)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, maternal autoantibodies, brain enlargement, brain volume, maternal immune activation, brain development, preschool children, ASD subtypes
- MeSH terms
- Adult, Autoantibodies, Brain, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Immunoglobulin G, Magnetic Resonance Imaging, Male, Organ Size
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