Objective: To explore possible associations between autism spectrum disorders (ASD) and environmental exposures, we linked the California autism surveillance system to estimated hazardous air pollutant (HAP) concentrations compiled by the U.S. Our results of a significantly reduced peripheral level of esRAGE coupled with elevated S100A9 point to a subtle but definite dysfunction of the AGEs/RAGE axis in autism that could play a role in the pathophysiology of this disorder.
In autistic patients, there was a statistically significant positive correlation between CARS scores and S100A9 levels (r=0.49, P=0.035), but no significant correlation was seen between esRAGE and S100A9 values (r=-0.23, P=0.34).
Significantly reduced levels of esRAGE (P=0.0023) and elevated concentrations of S100A9 (P=0.0012) were found in ASD patients as compared to controls. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. To shed more light on the possible alterations of the AGEs-RAGE axis in autism, hereto we measured plasma levels of endogenous secretory RAGE (esRAGE) and its proinflammatory ligand S100A9 in 18 young adults with autistic spectrum disorder (ASD) and 18 age- and gender-matched healthy comparison subjects. Through their interaction with their putative receptor RAGE, AGEs can promote neuroinflammation, oxidative stress and neuronal degeneration. An excess accumulation of advanced glycation end products (AGEs) has been reported in autism brains.
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