title: Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism.
abstract: An excess accumulation of advanced glycation end products (AGEs) has been reported in autism brains. Through their interaction with their putative receptor RAGE, AGEs can promote neuroinflammation, oxidative stress and neuronal degeneration. 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. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. 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. 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). 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.
authors.affiliation: Department of Applied Health and Behavioural Sciences, Section of Psychiatry, University of Pavia, Pavia, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Boso
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Minoretti
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Arra
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Politi
authors.forename: Stefania
authors.initials: S
authors.lastname: Ucelli di Nemi
authors.forename: Francesco
authors.initials: F
authors.lastname: Barale
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D013223:Statistics as Topic
chemical_list: D040502:Calgranulin B; D017127:Glycation End Products, Advanced