Presence of GAD65 autoantibodies in the serum of children with autism or ADHD

Abstract

Antibodies against glutamic acid decarboxylase 65 (GAD65) have been detected in the serum of patients with several neurological disorders. The presence of antibodies against GAD65 has not yet been examined in the serum of patients with neurodevelopmental disorders such as autism or attention-deficit/hyperactivity disorder (ADHD). In this study, GAD65 antibodies and total IgG were assayed in the serum of normal subjects and patients diagnosed with autism or ADHD. GAD65 antibodies were detected in the serum of 15% of children with autism (N = 20), 27% of children with ADHD (N = 15) and of none of the controls (N = 14). The serum of 60% of autistic and 53% of ADHD patients reacted with Purkinje neurons in mouse cerebellum. Serum from 20% of ADHD patients reacted also with the cells in the molecular and granule cell layers and cells in the vicinity of the Purkinje neurons. No association was found between the titer of GAD65 antibodies and total IgG levels, and presence of seizures or mental retardation. None of the ADHD patients were diagnosed with mental retardation. Serum anti-GAD65 antibodies may be a common marker of subgroups of patients with autism and ADHD. Reactions of serum antibodies with the cells in the cerebellum in these patients suggest direct effects on brain function. The subgroup of children with autism and ADHD that tests positive for GAD65 antibodies needs further characterization in a larger study.

Anti-Ganglioside, Anti-Glutamate, and Anti-Gad Antibody Levels in Attention-Deficit Hyperactivity Disorder

“…In addition, there has been an increase in the number of studies evaluating autoimmunity in the etiology of psychiatric diseases such as obsessive compulsive disorder, Tourette syndrome, and anorexia nervosa (13)(14)(15). Antibodies against glutamate NMDA receptors, GAD, and gliadin are closely related to CNS disorders (16,18). Brain areas, in which auto-antibodies have a direct effect include the hypothalamus, hippocampus, amygdala, and limbic system components and these areas account for emotional response and memory.…”

“…In addition, there is an increasing body of evidence indicating that the autoimmune mechanism may play a role in the etiology of ADHD similar to studies on the etiology of other psychiatric disorders, such as schizophrenia, obsessive compulsive disorder, and anorexia nervosa (13)(14)(15). In one study, it was proposed that anti-GAD65 auto-antibodies may be associated with ADHD (16). It was shown that dopamine and glutamatergic pathways are involved in ADHD (17).…”

The Role of Thiamine in Autism

“…Glutamateδ-1 receptor knockout mice (GluD1 KO) were hyperactive and manifested fewer anxiety and depression-like behaviors in a forced swim test as well as robust aggression in the resident-intruder test [87]. Antibodies against glutamic acid decarboxylase 65 (GAD65) have been detected in the serum of patients with autism or ASD [88]. Mitochondrial aspartate/glutamate carrier SLC25A12 polymorphisms are strongly associated with autism [89][90], and thiamine deficiency results in the down-regulation of glutamate transporters in cultured astrocytes [91].…”

Immune Involvement in Autism Spectrum Disorder as a Basis for Animal Models

“…Such "autoantibodies" have been identified in plasma from mothers of ASD children and from ASD individuals themselves, and some have been shown to react against neural components, including myelin basic protein and GAD65 in cerebellar Purkinje cells [70][71][72]. Although the majority of these autoantibodies are also detected at some frequency in non-ASD, typical controls, particular maternal autoantibodies that react against fetal brain proteins at approximately 37 kDa and 73 kDa display high specificity to autism cases, with striking reproducibility across large experimental cohorts [70].…”