Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Background: Autism spectrum disorders (ASD) are etiologically complex and heterogeneous, and in many cases are thought to involve the interplay of genetic and environmental factors. Growing evidence suggests that immune dysfunction may play a role in ASD, including the presence of specific autoantibodies in both mothers and their affected children. Diverse targets have been suggested for these antibodies, ranging from neuronal targets to yet uncharacterized proteins. However, most studies have had inconsistent findings and there are few studies that have replicated any specific antigenic target.   In adults Anti-phospholipid antibodies are associated with cognitive, neuropsychiatric, and neuromotor impairments; however, little is known about their role is pediatric cases or their levels in ASD.

Objectives: In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in the plasma of young children with ASD compared to age matched typically developing (TD) controls and children with developmental disabilities (DD) other than ASD.

Methods: Plasma was isolated from acid-citrate dextrose Vacutainers and was assessed by commercial ELISA for antibody levels of anti-Cardiolipin, anti-Phosphoserine, and anti-β2-Glycoprotein 1 antibodies.   Participants included 54 children with ASD [median age 44.8 months (interquartile range 32.0–57.7], 45 males), 33 TD controls [40.6 months (27.7–53.6), 27 males] and 22 DD controls [41.7 months (25.7–57.8), 18 males].

Results:   Antibody levels for anti-Phosphoserine (p<0.01), and anti-β2-Glycoprotein 1 (p<0.001) were found to be significantly higher in children with ASD compared with TD and DD controls. Antibody levels of anti-Cardiolipin were significantly higher compared with TD controls (p<0.001), and although there was a trend to elevated levels in children with ASD compared with DD controls, this did not reach statistical significance after multiple correction.  In addition, increased levels of anti-phospholipid antibodies were found to associate with more severe behavior impairments as measured by the Aberrant Behavior Checklist (ABC), Mullen Scales of Early Learning (MSEL), and Vineland Adaptive Behavior Scales (VABS).

Conclusions: We found that levels of anti-Cardiolipin, β2-Glycoprotein 1, and anti-Phosphoserine antibodies were elevated in children with ASD compared with age matched TD and DD controls.  The increase in antibody levels was associated with impaired behaviors on the ABC or decreased cognitive and adaptive functions on the MSEL and VABS.  This study provides evidence for the production of anti-phospholipid antibodies in young children with ASD, as these antibodies have previously been associated with neuropsychiatric impairments, and suggests a unique avenue for investigation of potential future therapies in ASD.