Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders

Abstract

Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age = 5½ years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age = 3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted.

The Role of the Immune System in Autism Spectrum Disorder

“…The evidence strongly supports distinct roles for both maternal Croen et al, 2008b;Singer et al, 2008;Zimmerman et al, 2007) and patient (Henneberg et al, 1994;Libbey and Fujinami, 2010;Ryberg, 1982) autoantibodies in ASD, including an ability to affect structural brain development (Nordahl et al, 2013;Rossi et al, 2011). Offending antibodies of either origin appear to persist systemically for extended periods of time Piras et al, 2014;Singer et al, 2006;Zimmerman et al, 2007), and although there exists a correlation between the two there does appear to be at least some differences in effect (Piras et al, 2014).…”

Autoantibodies in Neuropsychiatric Disorders

“…A specific subgroup of GABAergic interneurons located in the V1 layer was identified as the specific target [194]. Controversially, another study suggested that this staining might be unspecific because immunoreactivity was detected using serum of both healthy controls and a ASD patient with the intriguing fact that the IgG seropositive ASD patients presented more severe behavior and emotional problems compared to the IgG seronegative ones [195].…”

Autoimmunity in Autism Spectrum Disorders

“…An important finding was reached by Wills research group (2009), they demonstrated that 21% the positive autoantibodies samples, reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al, 2009). Further more, Rossi et al, (2011), demonstrated that 42% of controls and subjects with ASD were positively immunoreactive to some neural element, such as, cerebellar Golgi, interneurons, molecular layer of the dentate gyrus, and neuronal nuclei. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems.…”