Inflammatory Profile in ASD Children with and without Functional Gastrointestinal Disorders
Objectives: The main objective of this project is the identification of immunological markers involved in the pathogenesis of a subgroup of children with ASD. We hypothesized that children with ASD and gastrointestinal symptoms will also have markers of a systemic pro-inflammatory status.
Methods: We recruited 4 groups of participants (3 to 10 years old), selected for by the presence or absence of ASD diagnosis and the presence/absence of gastrointestinal (GI) functional symptoms: 1) ASD + fGID , group 2) ASD no fGID, group 3) healthy controls (HC) + fGID, group 4) HC; mean age was 6.67 (±1.9). 90% were male. ASD was diagnosed following the AACAP recommendations (Volkmar, 2014) and fGID were assessed with the ROMA-III. Plasma and peripheral blood mononuclear cell (PBMC) inflammatory biomarkers were analyzed: plasma TNFa, IL-1b, IL-6, , IFNg, LPS, LBP, IL-10, CD26act, CD26 exp; PBMC levels of Tool-Like receptor-4 (TLR-4), TLR-2, Myeloid differentiation primary response gene 88 (MyD88), TIR-domain containing protein TRIF, NFKb and TLR-3.
Results: One way-analysis of variance (ANOVA) analyses were conducted to determine statistically significant differences between groups for each biomarker; post hoc Dunn's Multiple Comparison Test was used to identify group pairs differences. The following markers differed between groups: LBP (χ2=10.74; p=0.09), IL-10, CD26act (χ2=10.77; p=0.09), Tool-Like receptor-4 (TLR-4) (χ2=23.13; p=0.001), Myeloid differentiation primary response gene 88 (MyD88) (χ2=13.67; p=0.00), TRIF (χ2=16.15; p=0.00), TLR3 (χ2=8.76; p=0.03), NFKb (χ2=12.45; p=0.01). Post-hoc analysis showed that ASD+fGID and HC+fGID groups did not differ in any of the markers analyzed. Significant differences were detected in all other comparisons between groups for several inflammatory markers. Bivariate analyses were conducted in order to compare the levels of the different markers between subjects with ASD and without ASD and patients with and without fGID. Specific differences will be fully reported together with clinical correlates.
Conclusions: Very early markers of activation of the innate immune system is seen in patients with ASD irrespective of the presence of fGID. This may reflect a that may indicate a systemic pro-inflammatory status in these patients. The study of the immunological pathophysiology in warranted in ASD, in order to identify a subgroup within ASD that may benefit from specific interventions.