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Misguided antibodies change the course of brain development

Molecular Psychiatry volume 28, pages 1833–1835 (2023)Cite this article

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Autism spectrum disorder (ASD) is an increasingly diagnosed neurodevelopmental disorder with hypothesized causes including a range of genetic and environmental risk factors [1, 2]. Symptoms of ASD include altered communication, reduced interest in social interaction, and repetitive/stereotyped behaviors [2]. Numerous studies have identified maternal immune responses during pregnancy to be a risk factor for a child’s ASD diagnosis [3]. Among this body of literature is the finding that about 20% of mothers whose children are subsequently diagnosed with ASD have circulating autoantibodies (aAbs) against proteins critical for early development [4]. While there is growing interest in the role of maternal aAbs in ASD pathogenesis, the mechanistic link between maternal aAb exposure and altered offspring neurodevelopment remains unclear. A study from Bruce et al. in this issue sought to better characterize the long-term neurological impact of maternal aAb exposure on offspring brain maturation, neurometabolism, and behavior [5].

Antibodies are proteins generated as part of the adaptive immune response to limit destruction of host tissue by foreign agents, such as viruses, bacteria, or other harmful stimuli. Antibodies bind a target antigen—a region of the infectious agent—which functions to neutralize the harm, for example, as in blocking the spread of infection. Usually, B cells that produce antibodies which bind host proteins are eliminated to avoid the attack of host cells by the immune system. Sometimes though, misdirected attacks occur in which antibodies are generated against host tissue. These so-called autoantibodies typically do not wreak havoc in the adult brain as the blood-brain barrier (BBB) prevents their entry in the healthy state. However, aAbs from the mother can cross the placenta during development and have been shown to be reactive against fetal brain proteins [6].

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Authors and Affiliations

  1. Center for Brain Immunology and Glia (BIG), Department of Neuroscience, Charlottesville, VA, USA

    Kristine E. Zengeler & John R. Lukens

  2. Neuroscience Graduate Program, Charlottesville, VA, USA

    Kristine E. Zengeler & John R. Lukens

  3. Cell and Molecular Biology Training Program, School of Medicine, University of Virginia, Charlottesville, VA, USA

    Kristine E. Zengeler & John R. Lukens

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  1. Kristine E. Zengeler
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KEZ and JRL designed the paper, participated in writing and proofreading, and oversaw the entire process of paper preparation.

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Correspondence to Kristine E. Zengeler or John R. Lukens.

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Zengeler, K.E., Lukens, J.R. Misguided antibodies change the course of brain development. Mol Psychiatry 28, 1833–1835 (2023). https://doi.org/10.1038/s41380-023-02042-x

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