title: Mast cell activation and autism.
abstract: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits. Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins. A number of papers, mostly based on parental reporting on their children's health problems, suggest that ASD children may present with "allergic-like" problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. In utero inflammation can lead to preterm labor and has itself been strongly associated with adverse neurodevelopmental outcomes. Premature babies have about four times higher risk of developing ASD and are also more vulnerable to infections, while delayed development of their gut-blood-brain barriers makes exposure to potential neurotoxins likely. Perinatal mast cell activation by infectious, stress-related, environmental or allergic triggers can lead to release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in a subgroup of ASD patients. This article is part of a Special Issue entitled: Mast cells in inflammation.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
authors.forename: Asimenia
authors.initials: A
authors.lastname: Angelidou
authors.forename: Konstantinos-Dionysios
authors.initials: KD
authors.lastname: Alysandratos
authors.forename: Bodi
authors.initials: B
authors.lastname: Zhang
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Francis
authors.forename: Elena
authors.initials: E
authors.lastname: Toniato
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kalogeromitros
mesh_terms: D000818:Animals; D001007:Anxiety / Q000150:complications; D001812:Blood-Brain Barrier / Q000473:pathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D003430:Cross-Sectional Studies; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology*; D015995:Prevalence; D013315:Stress, Psychological / Q000150:complications