Abstract
BackgroundThe causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Immune factors and inflammation are hypothesized pathogenic influences, but have not been examined longitudinally.MethodsIn a cohort of 104 participants with autism, we performed an assessment of immune mediators such as cytokines, chemokines, or growth factors in serum and cerebrospinal fluid (n = 67) to determine potential influences of such mediators in autism.ResultsAs compared with 54 typically developing controls, we found no evidence of differences in the blood profile of immune mediators supportive of active systemic inflammation mechanisms in participants with autism. Some modulators of immune function (e.g., EGF and soluble CD40 ligand) were increased in the autism group; however, no evidence of group differences in traditional markers of active inflammation (e.g., IL-6, TNFα, IL-1β) were observed in the serum. Further, within-subject stability (measured by estimated intraclass correlations) of most analytes was low, indicating that a single measurement is not a reliable prospective indicator of concentration for most analytes. Additionally, in participants with autism, there was little correspondence between the blood and CSF profiles of cytokines, chemokines, and growth factors, suggesting that peripheral markers may not optimally reflect the immune status of the central nervous system. Although the relatively high fraction of intrathecal production of selected chemokines involved in monocyte/microglia function may suggest a possible relationship with the homeostatic role of microglia, control data are needed for further interpretation of its relevance in autism.ConclusionsThese longitudinal observations fail to provide support for the hypothesized role of disturbances in the expression of circulating cytokines and chemokines as an indicator of systemic inflammation in autism. ClinicalTrials.gov, NCT00298246.
Highlights
The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder
Evidence from the effects of maternal viral infections during pregnancy [14], an excess of autoimmune disorders in mothers of subjects with Autism spectrum disorder (ASD) or their families [15, 16], and the effects of environmental factors on the formation of the immune system [17] support the view that various types of disturbances of immune function play roles in the pathogenesis of ASD and the perpetuation of associated behavioral and neurological abnormalities
Participants were 104 children diagnosed with DSM-IVTR Autistic Disorder (AUT) and 54 typically developing controls (TYP), aged 2–7.99 years at initial evaluation (Table 1)
Summary
The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Risk for ASD is highly associated with genetic factors [3], but current evidence suggests that neurobiological abnormalities in ASD Both innate and adaptive branches of the immune system are involved in critical mechanisms of brain development, Pardo et al Molecular Autism (2017) 8:1 neuronal and cortical organization, developmental and adaptive synaptic plasticity, and critical stages of brain function that determine neurological and behavioral activity into adulthood [11]. Studies of cellular immunity found abnormal function and number of T cells, as well as a lower percentage of CD4 T cells and a skewed CD4:CD8 T cell ratio [9] These studies involved small samples, and more recent studies have demonstrated altered function in selected immune pathways and cell systems such as T regulatory cells and NK cells in subjects with ASD [18,19,20]
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