No Evidence of Antibodies against GAD65 and Other Specific Antigens in Children with Autism

Abstract

Background: The presence of autoantibodies has been proposed as evidence for a role of autoimmunity in autism. This report investigates the prevalence of autoantibodies in children with autism using the luciferase immunoprecipitation systems (LIPS) immunoassay technology. A panel of autoantibody targets against several known and candidate neurological autoantigens, autoimmune-associated autoantigens and viruses was employed.

Methods: Serological analysis was performed on typically developing children (n = 55), developmentally delayed children without autism (n = 24) and children diagnosed with autism (n=104). Autoantibodies were measured against glutamic acid decarboxylase-65 (GAD65), a CNS autoantigen proposed to be associated with autism and against Ro52, glial fibrillary acidic protein, tyrosine hydroxylase, aquaporin-4, and gamma-enolase, the mouse mammary tumor virus and the xenotropic murine leukemia virus. Antibody levels and seropositivity prevalence were analyzed for statistically significant differences between the three groups.

Results: The majority of the children (98%) were seronegative for all targets in the antigen panel. No GAD65 seropositive children were detected in the cohort. Several low level seropositive sera against several of the protein targets were identified in isolated children in each of the three groups, but there was no difference in prevalence.

Conclusion: Using this panel of antigens and a sensitive, robust assay, no evidence of unusual immunoreactivity was detected in children with autism, providing evidence against a role of autoimmunity against several previously implicated proteins in autism spectrum disorder pathogenesis.

General significance: The idea that autoantibodies represent an underlying cause or are biomarkers for autism pathophysiology is not supported by this report.

Fig. 1

Lack of autoantibodies against GAD65 and Ro52 in the ASD cohort. Autoantibody levels were evaluated for (A) GAD65 and (B) Ro52 in the cohort. Additional positive control serum samples from type I diabetes and systemic lupus erythematosus subjects were included for the detection of GAD65 and Ro52 autoantibodies, respectively. The light units (LU) plotted on the y-axis using a log₁₀ scale measure the autoantibody levels for each sample. The dotted lines represent the cut-off values for determining seropositivity for each autoantigen.