Maternal antibrain antibodies in autism

Andrew W Zimmerman1, Susan L Connors, Karla J Matteson

  • 1Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA. zimmerman@kennedykrieger.org

Insights

Mothers of children with autism show unique antibodies targeting prenatal brain proteins. These autoantibodies may cross the placenta, potentially influencing fetal brain development and autism pathogenesis.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing evidence linking it to systemic and neuroimmune mechanisms.
  • While genetics play a role, atypical prenatal maternal immune responses are also implicated in autism pathogenesis.
  • Understanding prenatal immune factors is crucial for elucidating autism's origins.

Purpose of the Study:

  • To investigate serum antibody reactivity in mothers and children with autism against prenatal, postnatal, and adult rat brain proteins.
  • To identify specific prenatal antigens targeted by maternal antibodies in autism.
  • To explore the potential role of maternal autoantibodies in the prenatal development of autism.

Main Methods:

  • Serum samples from 11 mothers and their autistic children, maternal controls, and various control groups were analyzed.
  • Immunoblotting techniques were used to test serum reactivity against prenatal (gestational day 18), postnatal (day 8), and adult rat brain proteins.
  • Specific antigens, including myelin basic protein (MBP) and glial acidic fibrillary protein (GFAP), were used to identify antibody targets.

Main Results:

  • Similar antibody reactivity patterns to prenatal (day 18) rat brain proteins were observed in autistic children, their mothers, and children with other neurodevelopmental disorders.
  • These reactivity patterns differed significantly from those in mothers of typically developing children, normal siblings, and normal child controls.
  • Antibody reactivity persisted in mothers' sera for 2–18 years post-birth and was not linked to birth order; MBP and GFAP were not identified as targets.

Conclusions:

  • Specific serum antibodies recognizing prenatally expressed brain antigens are present in mothers of children with autism.
  • These maternal autoantibodies may cross the placenta, potentially impacting fetal brain development.
  • The findings suggest a potential prenatal immune-mediated mechanism contributing to autism pathogenesis.

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