Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder

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.

Peripheral Inflammatory Markers Contributing to Comorbidities in Autism

“…Differences have been reported by other studies, like those published by Saresella and Napoleoni [62,63], which referred to the influence of environmental stimulus acting to induce neurotoxicity. This process could affect the natural “pruning process” of apoptosis, which is essentially necessary to the formation of optimal neural pathways during the early stages of typical development, a feature to consider for future research projects.…”

“…This process could affect the natural “pruning process” of apoptosis, which is essentially necessary to the formation of optimal neural pathways during the early stages of typical development, a feature to consider for future research projects. The great complexity of abnormal brain architecture, the dysregulated synaptic plasticity and the aberrant heterogeneity of the immune reaction occurring in this disorder [31,62,63] are main elements to explore to depth of this pathology. Nevertheless, clinical protocols continue to be necessary to obtain major comprehension on the altered neural plasticity and behavioral features of these patients.…”

Therapeutic properties of mesenchymal stem cells for autism spectrum disorders

“…With many of these studies showing that as immune activation increases there is a correlation to more impaired behavior [29,30]. Similarly, a few studies have focused on the role of autoantibodies in autism and their relationship with behavior [31][32][33].…”

Exploring the Potential Role of Inflammation as an Etiological Process in ASD

“…Indeed, IL-1β, TNF-α, and TGF-β have been reported to induce inflammation, fever, and tissue destruction, and in extreme cases may lead to death in humans (Dinarello 2000). While several classes of cytokines have been identified in ASD, there appears to be nonsignificant differences between plasmacytokine levels in children with ASD and their typically developing siblings (Napolioni et al 2013). These results suggest that specific classes of cytokines and ultimate inflammatory state may be unique to the clinical presentation of ASD.…”