Inflammatory Biomarkers are Correlated with Some Forms of Regressive Autism Spectrum Disorder

Abstract

Background: Several studies have tried to investigate the role of inflammatory biomarkers in Autism Spectrum Disorder (ASD), and their correlations with clinical phenotypes. Despite the growing research in this topic, existing data are mostly contradictory. Methods: Eighty-five ASD preschoolers were assessed for developmental level, adaptive functioning, gastrointestinal (GI), socio-communicative and psychopathological symptoms. Plasma levels of leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), macrophage chemoattractant protein-1 (CCL2), tumor necrosis factor-alfa (TNF-α), and interleukin-6 (IL-6) were correlated with clinical scores and were compared among different ASD subgroups according to the presence or absence of: (i) GI symptoms, (ii) regressive onset of autism. Results: Proinflammatory cytokines (TNF-α, IL-6 and CCL2) were lower than those reported in previous studies in children with systemic inflammatory conditions. GI symptoms were not correlated with levels of inflammatory biomarkers except for resistin that was lower in ASD-GI children (p = 0.032). Resistin and PAI-1 levels were significantly higher in the group with “regression plus a developmental delay” onset (Reg+DD group) compared to groups without regression or with regression without a developmental delay (p < 0.01 for all). Conclusions: Our results did not highlight the presence of any systemic inflammatory state in ASD subjects neither disentangling children with/without GI symptoms. The Reg + DD group significantly differed from others in some plasmatic values, but these differences failed to discriminate the subgroups as possible distinct ASD endo-phenotypes.

Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial

“…In fact, in the current study, the supplementation with DSF compared with placebo resulted in no significant effects on the levels of plasma and fecal inflammatory biomarkers. In a previous investigation, we have reported that the values of these biomarkers were in the normal range already at baseline ( 51 ); thus, we do not confirm the two previous studies ( 52 , 53 ) reporting some positive effects of probiotics on biomarkers of inflammation, and we could hypothesize that the effect of probiotics on adaptative functioning is not mediated by a reduction in systemic or intestinal inflammation.…”

Epigenetic clock analysis and increased plasminogen activator inhibitor-1 in high-functioning autism spectrum disorder

“…Our finding of increased DNAmPAI-1 in individuals with ASD may support this hypothesis. Moreover, plasma PAI-1 levels were significantly higher in individuals with ASD and both regression and a developmental delay compared to individuals with ASD without regression, or individuals with ASD and regression without a developmental delay [ 43 ]. In contrast, no association was observed between ASD and the 4G/5G sequence polymorphism in the PAI-1 gene promoter that influences the level of plasma PAI-1 [ 44 ].…”

The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: a systematic review

“…There are great controversies regarding the role of pro-inflammatory cytokines in ASD. Despite the presence of a specific plasmatic cytokine profile in children with regressive ASD, recently, Prosperi et al [ 67 ] did not support the use of cytokines as markers of leaky gut and did not support anti-inflammatory therapies in ASD-affected children. They recommended the search of alternative hypotheses for the etiology of GI symptoms in ASD-affected individuals.…”