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Biomarkers Linked to Autism Risk Identified

By LabMedica International staff writers
Posted on 20 Jan 2022
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Image: The Human Cytokine/Chemokine/Growth Factor Convenience 45-Plex ProcartaPlex Panel, 384 well (lyophilized beads) enables the study of immune function by analyzing 45 protein targets in a single well using Luminex FLEXMAP 3D and INTELLIFLEX instruments (Photo courtesy of Thermo Fisher Scientific)
Image: The Human Cytokine/Chemokine/Growth Factor Convenience 45-Plex ProcartaPlex Panel, 384 well (lyophilized beads) enables the study of immune function by analyzing 45 protein targets in a single well using Luminex FLEXMAP 3D and INTELLIFLEX instruments (Photo courtesy of Thermo Fisher Scientific)
Autism spectrum disorders (ASDs) comprise a set of pervasive neurodevelopmental conditions characterized by restricted and repetitive behavior patterns and impairments in social interaction and communication.

Cytokines regulate intrauterine immune responses, neurogenesis, neuronal migration, and synaptogenesis, and have the capacity to signal through cognate receptors on microglial cells and other neural components distributed throughout brain circuitry.

An international team of Infection and Immunology Specialists led by those at Columbia University (New York, NY, USA) identified molecular signatures of gestational inflammation linked to the risk of developing autism spectrum disorder (ASD). They analyzed the presence of 60 molecular markers of immune response, including cytokines and growth factors. Blood samples were collected during pregnancy (maternal mid-gestational blood sample) and at birth (cord blood) from 957 children, roughly half of whom were later diagnosed with ASD.

The team assayed a wide range of cytokines, chemokines, cellular, and growth factors reflecting key processes relating to systemic activation of inflammatory/immune signaling pathways involved in autoimmunity and anti-inflammatory responses as well as others implicated in CNS inflammation, neurovascular disruption, and neurogenesis. Immune molecules within this panel are also found to be dysregulated during infection with certain pathogens, including those that trigger autoimmunity, as well as in some studies in ASD. The scientists used a customized Procarta immunoassay (Affymetrix/eBioscience, Santa Clara, CA, USA). ProcartaPlex immunoassays are antibody-based, magnetic bead reagent kits and panels for multiplex protein quantitation using the Luminex instrument platform (Austin, TX, USA).

The investigator reported that their study linked ASD risk to groupings of inflammation-related molecules, with different groupings seen in boys versus girls. Among the most predictive molecules were interleukins like IL1RA and IL4. Four molecules thought to be involved in fetal brain development were also linked to ASD risk in both sexes: TNFα, Serpin E1, VCAM1, and IL1β. Biomarkers collected at birth were only slightly less predictive than those collected during pregnancy.

Mady Hornig, MD, an associate professor and a co-first author of the study, said, “We found immune signatures in mid-pregnancy blood samples from mothers and in umbilical cord blood from children later diagnosed with autism that correlate with responses to infection, and molecules important for the development of the brain and its blood supply.”

The authors concluded that their results provide robust evidence of immune dysregulation in mothers as early as 17–21 weeks gestation and in cord blood (CB) of neonates later diagnosed with ASD. The study was published on January 5, 2022 in the journal Molecular Psychiatry.

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