Increased Anti-Phospholipid Antibodies in Autism Spectrum Disorders

Abstract

Autism spectrum disorders (ASD) are characterized by impairments in communication, social interactions, and repetitive behaviors. While the etiology of ASD is complex and likely involves the interplay of genetic and environmental factors, growing evidence suggests that immune dysfunction and the presence of autoimmune responses including autoantibodies may play a role in ASD. Anti-phospholipid antibodies are believed to occur from both genetic and environmental factors and have been linked to a number of neuropsychiatric symptoms such as cognitive impairments, anxiety, and repetitive behaviors. In the current study, we investigated whether there were elevated levels of anti-phospholipid antibodies in a cross-sectional analysis of plasma of young children with ASD compared to age-matched typically developing (TD) controls and children with developmental delays (DD) other than ASD. 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. Further, the increase in antibody levels was associated with more impaired behaviors reported by parents. This study provides the first evidence for elevated production of anti-phospholipid antibodies in young children with ASD and provides a unique avenue for future research into determining possible pathogenic mechanisms that may underlie some cases of ASD.

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

“…For instance, a lower concentration of cardiolipin, the critical component of the inner mitochondrial membrane, in SZ (Fig. 5c) matches elevated anti-cardiolipin antibody levels reported in SZ patients [73,74]. Similarly, elevated levels of triradylglycerols (TG) in DS match the reported overexpression of genes involved in energy consumption and oxidative stress in DS patients [75], as TGs represent one of the major energy sources [76], and were linked to an increase of lipid peroxidation markers [77].…”

Antipurinergic therapy corrects the autism-like features in the Fragile X (Fmr1 knockout) mouse model

“…We found plasma cardiolipin was therapeutically downregulated by suramin. Although elevations in plasma cardiolipin species have not yet been reported in children with autism, anti-cardiolipin antibodies have [ 88 ].…”

Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations

“…Activation of the immune system may also lead to production of anti-phospholipid antibodies (APLAs). Increased levels of APLAs (e.g., anti-cardiolipin, β2-glycoprotein 1, and anti-phosphoserine), which are normally associated with increased risk of blood clotting and pregnancy losses, have been identified in the plasma of young (age range 24–82 months) children with ASD and associated with their impaired behavior [ 114 ].…”