title: Multiple inflammasome complexes are activated in autistic spectrum disorders.
abstract: BACKGROUND
  Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation.
  
  
  METHODS
  The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC).
  
  
  RESULTS
  A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS.
  
  
  CONCLUSIONS
  These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD.
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy. Electronic address: msaresella@dongnocchi.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Zoppis
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Hernis
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Zanette
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milano, Milano, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.affiliation: Child Neurology and Psychiatry Unit, C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Chiappedi
authors.affiliation: Department of Experimental, Diagnostic, Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ghezzo
authors.affiliation: Department of Science of Health, University of Milano, Milano, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: la Rosa
authors.affiliation: Department of Physiopathology and Transplants, University of Milano, Milano, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milano, Italy; Department of Physiopathology and Transplants, University of Milano, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000067877:Autism Spectrum Disorder / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000097:blood*; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D005767:Gastrointestinal Diseases / Q000097:blood*; D006801:Humans; D058847:Inflammasomes / Q000097:blood*; D007249:Inflammation / Q000097:blood*; D007378:Interleukins / Q000097:blood*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000097:blood*
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D058847:Inflammasomes; D007378:Interleukins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: Autistic spectrum disorders (ASD); IFABP; Inflammasome; NLRP3; Neuroinflammation