Evidence increasingly supports the notion of an autoimmune version of autism, and a new study involving specific autoantibodies that are directed at fetal brain tissue and that are found in a modest proportion of mothers with an autistic child, bolsters this theory.
In an earlier study, researchers at the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at the University of California, Davis, demonstrated that 12% of women with an autistic child had "unusual" antibodies not present in mothers of typically developing children or in mothers of children with other intellectual developmental disorders. Since this raised the hypothesis that the antibodies, which were immunoglobulin G and thus cross the placenta, might be interacting with the fetal brain, leading to disregulation of development (and ultimately to autism), the researchers expanded their study by testing the effects of the antibodies in pregnant Rhesus monkeys.
They found that the offspring of monkeys injected with the IgG showed distinctive autistic characteristics, David G. Amaral, Ph.D., research director at the MIND Institute, reported at the annual meeting of the American College of Neuropsychopharmacology.
Specifically, pregnant monkeys were injected over a 6-week period with either purified autoantibodies to fetal brain proteins from the blood of the mothers of children with autism, or with autoantibodies from mothers with typically developing children. The offspring of the monkeys injected with autoantibodies from mothers with an autistic child – but not those injected with samples from mothers of typically developing children, demonstrated social impairment and stereotypic behaviors across several behavioral testing paradigms, Dr. Amaral said during a press briefing held in conjunction with the meeting.
The social impairment as detected by blinded investigators was subtle and did not reach the level of social impairment consistent with autism, but the stereotypy was profound.
"Given that (stereotypy) is one of the clinical signs of autism, we thought this was intriguing," he said, adding: "The ability to reproduce this effect in an animal model was strong evidence that these antibodies may have a disease-causing effect."
Dr. Amaral and his colleagues have replicated these findings in two independent studies, and are currently extending their analysis to a magnetic resonance imaging study of brain development in the treated monkeys. In other prior research by the MIND Institute investigators, a substantial proportion of boys with autism have been shown to have precocious brain growth during early childhood, and the MRI studies are designed to determine if similar patterns of brain development occur in the treated Rhesus monkeys.
If confirmed, the findings of this study could lead to screening tests for pregnant mothers, and perhaps to preventive measures for certain types of autism.
For example, if the researchers successfully segment an autoimmune version of autism as a uniform, homogenous version, unique preventive measures and treatment options could be developed, Dr. Amaral explained.
Currently an estimated 1% of children in the United States have an autism-spectrum disorder, and the probability of a mother with an autistic child having a subsequent child with autism is 25% if the subsequent child is a boy, and 9% if the child is a girl. The ability to test for antibodies against fetal brain tissue in pregnant mothers who already have a child with autism could lead to earlier recognition of the disorder in the second child, and to interventions that prevent or reduce the effects of the harmful antibodies, he said.
"What’s intriguing about this line of work is that in the majority of autism we don’t have a lot of targets for intervention or prevention, whereas if this were to be replicated and pan out, these antibodies are quite easy to identify," he added.
Dr. Amaral said he had no disclosures.