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Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis
Rut Mazón-Cabrera1, Jori Liesenborgs2, Bert Brône3
1Department of Immunology and Infection, Biomedical Research Institute, UHasselt, Transnational University Limburg, Diepenbeek, Belgium.
Insights
Researchers identified novel maternal autoantibodies targeting fetal brain proteins in mothers of children with autism spectrum disorder (ASD). These autoantibodies show potential as early biomarkers for ASD screening and diagnosis.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with challenges in early diagnosis.
- Maternal autoantibodies against fetal brain antigens are implicated in ASD neurodevelopment.
- Identifying these autoantibodies is crucial for developing diagnostic tools.
Purpose of the Study:
- To identify novel maternal autoantibodies reactive against human fetal brain antigens.
- To explore the utility of these autoantibodies as biomarkers for ASD screening and diagnosis.
Main Methods:
- A human fetal brain cDNA phage display library was constructed and screened.
- Antibody reactivity was assessed in plasma samples from mothers of children with ASD (m-ASD) and mothers of typically developing children (m-TD).
Main Results:
- Six novel University Hasselt (UH)-ASD antigens were identified, including RPL23, GAPDH, and CAMSAP3.
- Antibody reactivity against a panel of four UH-ASD antigens was observed in 16% of m-ASD samples versus 4% of m-TD samples (p = 0.0049).
Conclusions:
- Maternal autoantibodies against specific UH-ASD antigens represent a potential novel biomarker for ASD.
- These findings could support the development of new tools for ASD diagnosis in a subset of individuals.
Introduction:
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which early recognition is a major challenge. Autoantibodies against fetal brain antigens have been found in the blood of mothers of children with ASD (m-ASD) and can be transferred to the fetus where they can impact neurodevelopment by binding to fetal brain proteins. This study aims to identify novel maternal autoantibodies reactive against human fetal brain antigens, and explore their use as biomarkers for ASD screening and diagnosis.
Methods:
A custom-made human fetal brain cDNA phage display library was constructed, and screened for antibody reactivity in m-ASD samples from the Simons Simplex Collection (SSC) of the Simons Foundation Autism Research Initiative (SFARI). Antibody reactivity against 6 identified antigens was determined in plasma samples of 238 m-ASD and 90 mothers with typically developing children (m-TD).
Results:
We identified antibodies to 6 novel University Hasselt (UH)-ASD antigens, including three novel m-ASD autoantigens, i.e., ribosomal protein L23 (RPL23), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and calmodulin-regulated spectrin-associated protein 3 (CAMSAP3). Antibody reactivity against a panel of four of these targets was found in 16% of m-ASD samples, compared to 4% in m-TD samples (p = 0.0049).
Discussion:
Maternal antibodies against 4 UH-ASD antigens could therefore provide a novel tool to support the diagnosis of ASD in a subset of individuals.
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