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Immune mediators in the brain and peripheral tissues in autism spectrum disorder.

ABSTRACT: Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors--including autoimmunity, infection and fetal reactive antibodies--are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways--including pathways downstream of cytokines, the receptor MET, major histocompatibility complex class I molecules, microglia and complement factors--have been identified that link immune activation to ASD phenotypes. Together, these findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors.

SUBMITTER: Estes ML

PROVIDER: S-EPMC5650494 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Immune mediators in the brain and peripheral tissues in autism spectrum disorder.

Estes Myka L ML McAllister A Kimberley AK

Nature reviews. Neuroscience 20150801 8

Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors--including autoimmunity, infection and fetal reactive antibodies--are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways--including path ...[more]

PMID: 26189694

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Project description:BackgroundAutism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM2.5) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children.ObjectivesThis study examined interactions between MIA-related conditions and prenatal PM2.5 or major PM2.5 components on ASD risk.MethodsIn a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM2.5 and four PM2.5 components, black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates.ResultsASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM2.5 [1.07; 1.03-1.12 per interquartile (3.73 μg/m3) increase] and with all four PM2.5 components. However, there were no interactions of each category of MIA-related conditions with PM2.5 or its components on either multiplicative or additive scales.ConclusionsMIA-related conditions and pregnancy PM2.5 were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM2.5 exposure with ASD risk.

Dataset Information

Immune mediators in the brain and peripheral tissues in autism spectrum disorder.

Publications

Immune mediators in the brain and peripheral tissues in autism spectrum disorder.

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