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Maternal autoantibody related autism: mechanisms and pathways

Molecular Psychiatry volume 24, pages 252–265 (2019)Cite this article

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Abstract

It has been estimated that autism spectrum disorder (ASD) now affects 1 in 59 children in the United States. Although the cause(s) of ASD remain largely unknown, it is becoming increasingly apparent that ASD can no longer be defined simply as a behavioral disorder, but is in effect a rather complex and highly heterogeneous biological disorder. Up until recently the brain was thought to be “immune privileged.” However, it is now known that the immune system plays critical roles in the development and functioning of the brain throughout life. Recent evidence from multiple investigators has illustrated the deleterious role that dysregulation of the maternal immune system during gestation can play in the manifestation of changes in neurodevelopment, resulting in the development of neurobehavioral disorders such as ASD. One potential etiologic pathway through which the maternal immune system can interfere with neurodevelopment is through maternal autoantibodies that recognize proteins in the developing fetal brain. This mechanism of pathogenesis is now thought to lead to a subphenotype of ASD that has been termed maternal autoantibody related (MAR) ASD. This review provides an overview of the current research implicating the presence of brain-reactive maternal autoantibodies as a risk factor for MAR ASD.

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Acknowledgements

We thank the staff of the CHARGE study, and all of the families involved in this research.

Funding

This study was funded by the NIEHS Center for Children’s Environmental Health and Environmental Protection Agency (EPA) grants (2P01ES011269-11, 83543201 respectively), the NIEHS-funded CHARGE study (R01ES015359), the NICHD funded IDDRC 054 (U54HD079125), and the Hartwell and Hearst Foundations.

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  1. Rheumatology/Allergy and Clinical Immunology, University of California, 451 E. Health Sciences Drive, Suite 6510 GBSF, Davis, CA, 95616, USA

    Karen L. Jones & Judy Van de Water

  2. The M.I.N.D. Institute, University of California, Davis, CA, 95616, USA

    Karen L. Jones & Judy Van de Water

  3. NIEHS Center for Children’s Environmental Health, University of California, Davis, CA, 95616, USA

    Judy Van de Water

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Correspondence to Judy Van de Water.

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Conflict of interest

VdW is the founder of a startup company that will focus on the development of the MAR ASD autoantibody profile as an assessment of risk for a child developing ASD. VdW received consulting fees from Pediatric Bioscience (no longer in operation) from Jan 1, 2015 until October 2015. The remaining authors declare no conflict of interest.

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Jones, K.L., Van de Water, J. Maternal autoantibody related autism: mechanisms and pathways. Mol Psychiatry 24, 252–265 (2019). https://doi.org/10.1038/s41380-018-0099-0

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