Abstract
ObjectiveConverging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other developmental disorders. In the current study, we used plasma-cytokine profiling for 25 discordant sibling pairs to evaluate whether these alterations occur within families with ASD.MethodsPlasma-cytokine profiling was conducted using an array-based multiplex sandwich ELISA for simultaneous quantitative measurement of 40 unique targets. We also analyzed the correlations between cytokine levels and clinically relevant quantitative traits (Vineland Adaptive Behavior Scale in Autism (VABS) composite score, Social Responsiveness Scale (SRS) total T score, head circumference, and full intelligence quotient (IQ)). In addition, because of the high phenotypic heterogeneity of ASD, we defined four subgroups of subjects (those who were non-verbal, those with gastrointestinal issues, those with regressive autism, and those with a history of allergies), which encompass common and/or recurrent endophenotypes in ASD, and tested the cytokine levels in each group.ResultsNone of the measured parameters showed significant differences between children with ASD and their related typically developing siblings. However, specific target levels did correlate with quantitative clinical traits, and these were significantly different when the ASD subgroups were analyzed. It is notable that these differences seem to be attributable to a predisposing immunogenetic background, as no other significant differences were noticed between discordant sibling pairs. Interleukin-1β appears to be the cytokine most involved in quantitative traits and clinical subgroups of ASD.ConclusionsIn the present study, we found a lack of significant differences in plasma-cytokine levels between children with ASD and in their related non-autistic siblings. Thus, our results support the evidence that the immune profiles of children with autism do not differ from their typically developing siblings. However, the significant association of cytokine levels with the quantitative traits and the clinical subgroups analyzed suggests that altered immune responses may affect core feature of ASD.
Highlights
Autism spectrum disorders (ASDs) are a heterogeneous group of severe neurodevelopmental disorders characterized by atypical social interactions, impaired communication, and tendency to engage in idiosyncratic, repetitive, orIn addition to the results from neurobiological research in autism spectrum disorder (ASD), highlighting the pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition, and behavior, converging evidence point to the existence of altered immune function in ASD, which directly affects some or all these neurological processes [4]
There was no significant difference in age distribution between children with ASD and their healthy siblings (z = 1.232, P = 0.218)
We found increased levels of IL-1β, IL-5, and IL-17, together with total Th2 and Th17 cytokine levels, in children with regressive ASD compared with children with ASD who had no regression
Summary
Autism spectrum disorders (ASDs) are a heterogeneous group of severe neurodevelopmental disorders characterized by atypical social interactions, impaired communication, and tendency to engage in idiosyncratic, repetitive, orIn addition to the results from neurobiological research in ASD, highlighting the pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition, and behavior, converging evidence point to the existence of altered immune function in ASD, which directly affects some or all these neurological processes [4]. Previous studies [14,15,16,17,18,19,20,21,22,23,24,25] have reported altered cytokine levels in subjects with autism with inconclusive results, perhaps attributable to different types of study design, and probably reflecting the wide heterogeneity of ASD. Previous studies have shown that patients with autism have higher cytokine levels in cases of autism compared with controls or subjects with other developmental disorders [14,15,16,17,18,19,20,21,22,23,24,25]. Because of the high phenotypic heterogeneity of ASD, we divided the patients into four defined subgroups (those who were non-verbal, those with gastrointestinal (GI) issues, those with regressive autism, and those with a history of allergies), which encompass common and/or recurrent endophenotypes in ASD, and tested the cytokine levels of these groups [27,28,29,30]
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