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An Exploratory Examination of Neonatal Cytokines and Chemokines as Predictors of Autism Risk: The Early Markers for
Luke S Heuer1, Lisa A Croen2, Karen L Jones1
1Division of Rheumatology, Allergy, and Clinical Immunology, Department of Internal Medicine, University of California, Davis, Davis, California; MIND Institute, University of California, Davis, Davis, California.
Insights
Early detection of autism spectrum disorder (ASD) may be possible through neonatal bloodspot testing. Elevated inflammatory markers like IL-8 in newborns indicate a higher risk for ASD.
Area of Science:
- Immunology
- Neurodevelopmental Disorders
- Biomarker Discovery
Background:
- Early identification of autism spectrum disorder (ASD) is crucial for timely intervention and improved outcomes.
- Current diagnostic methods often occur after developmental differences become apparent.
Purpose of the Study:
- To investigate neonatal immune markers as potential early biomarkers for ASD.
- To assess differences in cytokine and chemokine levels in newborns later diagnosed with ASD.
Main Methods:
- Analysis of 42 immune markers in newborn bloodspots from children with ASD, developmental delay, and general population controls.
- Utilized Luminex multiplex platform and statistical analyses including logistic regression and PLS-DA.
Main Results:
- Children with ASD showed significantly higher neonatal levels of interleukin-6 (IL-6) and IL-8 compared to controls.
- Elevated IL-8 was particularly significant in early-onset ASD cases.
- Increased levels of eotaxin-1, interferon-γ, and IL-12p70 were observed in ASD cases versus developmental delay cases.
Conclusions:
- Neonatal immune activation, indicated by elevated inflammatory markers, is associated with a higher risk of ASD.
- Neonatal bloodspot testing for cytokine/chemokine levels shows promise for identifying ASD risk at birth.
Background:
The identification of an early biomarker for autism spectrum disorder (ASD) would improve the determination of risk, leading to earlier diagnosis and, potentially, earlier intervention and improved outcomes.
Methods:
Data were generated from the Early Markers for Autism study, a population-based case-control study of prenatal and neonatal biomarkers of ASD. Newborn bloodspots of children with ASD (n = 370), children with developmental delay (n = 140), and general population (GP) controls (n = 378) were analyzed for 42 different immune markers using a Luminex multiplex platform. Comparisons of immune marker concentrations between groups were examined using logistic regression and partial least squares discriminant analysis.
Results:
Children with ASD had significantly increased neonatal levels of interleukin-6 (IL-6) and IL-8 compared with GP controls. An increase in IL-8 was especially significant in the ASD group with early onset compared with the GP group, with an adjusted odds ratio of 1.97 (95% confidence interval, 1.39-2.83; p = .00014). In addition, children with ASD had significantly elevated levels of eotaxin-1, interferon-γ, and IL-12p70 relative to children with developmental delay. We observed no significant differences in levels of immune markers between the developmental delay and GP groups.
Conclusions:
Elevated levels of some inflammatory markers in newborn bloodspots indicated a higher degree of immune activation at birth in children who were subsequently diagnosed with ASD. The data from this exploratory study suggest that with further expansion, the development of neonatal bloodspot testing for cytokine/chemokine levels might lead to the identification of biomarkers that provide an accurate assessment of ASD risk at birth.
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