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Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder.

Abstract：

OBJECTIVE:Converging 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. METHODS:Plasma-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. RESULTS:None 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. CONCLUSIONS:In 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.

journal_name

J Neuroinflammation

journal_title

Journal of neuroinflammation

authors

Napolioni V,Ober-Reynolds B,Szelinger S,Corneveaux JJ,Pawlowski T,Ober-Reynolds S,Kirwan J,Persico AM,Melmed RD,Craig DW,Smith CJ,Huentelman MJ

doi

10.1186/1742-2094-10-38

subject

Has Abstract

pub_date

2013-03-14 00:00:00

pages

issn

1742-2094

pii

1742-2094-10-38

journal_volume

pub_type

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Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder.