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Study IDs Brain Proteins Targeted by Autism-Associated Antibodies

Maternal antibodies may disrupt early brain development; findings could produce antibody-blocker treatments and risk-assessment test
July 09, 2013


In 2008, researchers found antibodies to fetal brain proteins in the blood of some women whose children developed autism. The discovery suggested that such antibodies might contribute to autism spectrum disorder (ASD) by interfering with brain development during pregnancy.

Today, the research team reports that they’ve identified the specific brain proteins targeted by several of these maternal antibodies. The proteins play key roles in brain development and brain-cell connections. If confirmed, the findings could lead to treatments that block the antibodies’ harmful activity during pregnancy. Already, the team is developing a  test that would scan for antibodies in a mother’s blood to gauge whether her young child might benefit from early therapy before the outward symptoms of autism appear.

The report appears today in the journal Translational Psychiatry. Immunologist Judy Van de Water, of the University of California-Davis MIND Institute, is the senior author. Autism Speaks helped fund the research with a graduate fellowship for lead investigator Daniel Braunschweig.

“Since the original discovery of an autoantibody marker in the blood of some women who have a child affected with autism, research has focused on how to use this finding for better diagnosis and intervention of ASD,” comments Alycia Halladay, Autism Speaks senior director of environmental and clinical sciences. “This new study is an important step in that process. It identifies risks of ASD based on reactivity to these specific proteins.” 

Antibodies gone awry
Antibodies are immune-system chemicals that normally target microbes and other “foreign invaders” for destruction. When antibodies mistakenly target healthy tissues, auto-immune disorders can result. Researchers and physicians have long known that a mother’s antibodies cross the placenta during pregnancy. Indeed, they protect babies from infection until their own immune systems start creating antibodies. But as with any type of antibody, maternal antibodies can cause problems when they turn against "self."

To identify the brain proteins targeted by the implicated antibodies, the investigators tested blood samples from 246 mothers whose children developed autism and 149 mothers whose children did not develop the disorder. On average, the blood from the mothers of children with autism was 21 times more likely to react with seven fetal brain proteins than was the blood of the other mothers. In all, nearly a quarter of the mothers with affected children had some combination of antibodies to these proteins. By contrast, this was true of less than 1 percent of the mothers whose children did not develop the disorder.

“All of the target proteins are found in abundance in the fetal brain during pregnancy and play important roles in brain development,” says Dr. Van de Water. “Now we will be able to better determine the role of each of these antibodies in changing brain development.”

Maternal antibodies cross the placenta early in pregnancy. At birth, their concentration is even greater in the newborn than in the mother. They remain in the baby’s bloodstream for about six months, after which the baby’s own immune system takes over.

"It’s important to note that women have no control over whether or not they develop these autoantibodies," Dr. Van de Water says. "As with other autoimmune disorders, we do not know what the initial trigger is that leads to their production."

Potential treatments and risk testing
The researchers are currently developing a risk-assessment test based on the antibody combinations they discovered. Potentially, it could be used by mothers of young children who are showing signs of developmental delay, to further flag their need for early behavioral therapy.

Potential preventive treatments might include medicines given to the mother during pregnancy to block the antibodies’ harmful action. In addition, further study of the proteins and the brain pathways they affect may help researchers better understand the causes of autism and lead to other new therapies.

In a companion piece in the same issue of the journal, a related research team describe treating pregnant rhesus monkeys with the maternal antibodies. When studying the brain development and behavior of the offspring, they found clear autism-like changes.

“Together, these two studies offer new evidence of the role of antibodies in brain development and autism symptoms,” Dr. Halladay says.

Dr. Van de Water discusses her research findings in the UC-Davis video below.



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