Levels of soluble platelet endothelial cell adhesion molecule-1 and P-selectin are decreased in children with autism spectrum disorder

Abstract

Background: Although the etiopathology of autism spectrum disorder (ASD) is not clear, there is increasing evidence that dysfunction in the immune system affects many children with ASD. Findings of immune dysfunction in ASD include increases in inflammatory cytokines, chemokines, and microglial activity in brain tissue and cerebrospinal fluid, as well as abnormal peripheral immune cell function.

Methods: Adhesion molecules, such as platelet endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), P-selectin, and L-selectin, function to facilitate leukocyte transendothelial migration. We assessed concentrations of soluble adhesion molecules, sPECAM-1, sICAM-1, sVCAM-1, sP-selectin, and sL-selectin in the plasma of 49 participants with ASD and 31 typically developing controls of the same age, all of whom were enrolled as part of the Autism Phenome Project. Behavioral assessment, the levels of soluble adhesion molecules, and head circumference were compared in the same subjects.

Results: Levels of sPECAM-1 and sP-selectin were significantly reduced in the ASD group compared to typically developing controls (p < .02). Soluble PECAM-1 levels were negatively associated with repetitive behavior and abnormal brain growth in children with ASD (p = .03).

Conclusions: Because adhesion molecules modulate the permeability and signaling at the blood-brain barrier as well as leukocyte infiltration into the central nervous system, the current data suggest a role for these molecules in the complex pathophysiology of ASD.

Figure 1. Levels of soluble adhesion molecules in ASD and association with repetitive behavior

(A) Median levels (black horizontal bar) of sPECAM-1 are significantly lower in ASD (grey dots) in comparison with typically developing controls (white dots). (B, C) There was no difference in the median levels of sICAM-1, sVCAM-1 or sL-Selectin between ASD participants and controls. (D) sP-Selectin levels are significantly lower in the ASD group as compared with controls. (E) There was no difference in sL-Selectin levels between the two groups. (F) Correlation between sPECAM-1 levels and RBSR scores in ASD subjects. RBSR scores correlate negatively with PECAM-1 levels.