Do Alarmins Have a Potential Role in Autism Spectrum Disorders Pathogenesis and Progression?

Abstract

Autism spectrum disorders (ASDs) represent a disabling condition in early childhood. A number of risk factors were proposed in order to explain their pathogenesis. A multifactorial model was proposed, and data supported the implication of genetic and environmental factors. One of the most accepted speculations is the existence of an imbalance of the immune system. Altered levels of cytokines, chemokines and immunoglobulins were demonstrated in patients with ASDs; in particular, proinflammatory mediators were significantly increased. Alarmins are a multifunctional heterogeneous group of proteins, structurally belonging to specific cells or incorporated by them. They are released in the surrounding tissues as a consequence of cell damage or inflammation. Their functions are multiple as they could activate innate immunity or recruit and activate antigen-presenting cells stimulating an adaptive response. Alarmins are interesting both for understanding the inflammatory process and for diagnostic purposes as biomarkers. Moreover, recent studies, separately, showed that alarmins like interleukin (IL)-33, high-mobility group box 1 (HMGB1), heat-shock protein (HSP) and S100 protein (S100) could play a relevant role in the pathogenesis of ASDs. According to the literature, some of these alarmins could be suitable as biomarkers of inflammation in ASD. Other alarmins, by interfering with the immune system blocking pro-inflammatory mediators, could be the key for ameliorating symptoms and behaviours in autistic disorders.