Researchers find evidence of link between immune irregularities and autism

July 17, 2012, California Institute of Technology
A new Caltech study suggests that specific changes in an overactive immune system can contribute to autism-like behaviors in mice, and that in some cases, this activation can be related to what a developing fetus experiences in the womb. Credit: Elaine Hsiao

Scientists at the California Institute of Technology (Caltech) pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder.

What has remained unanswered, however, is whether the immune changes play a causative role in the development of the disease or are merely a side effect. Now a new Caltech study suggests that specific changes in an overactive can indeed contribute to autism-like behaviors in mice, and that in some cases, this activation can be related to what a experiences in the .

The results appear in a paper this week in the (PNAS).

"We have long suspected that the immune system plays a role in the development of ," says Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of at Caltech, who led the work. "In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring."

The first step in the work was establishing a mouse model that tied the autism-related behaviors together with immune changes. Several large —including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005—have found a correlation between viral infection during the first trimester of a mother's pregnancy and a higher risk for autism spectrum disorder in her child. To model this in mice, the researchers injected pregnant mothers with a viral mimic that triggered the same type of immune response a viral infection would.

"In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson's lab and lead author of the PNAS paper.

The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder—repetitive or stereotyped behaviors, decreased social interactions, and impaired communication. In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.

Next, the researchers characterized the immune system of the offspring of mothers that had been infected and found that the offspring display a number of immune changes. Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a key role in suppressing the immune response. Taken together, the observed immune alterations add up to an immune system in overdrive—one that promotes inflammation.

"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. "This tells us that a prenatal challenge can result in long-term consequences for health and development."

With the established, the group was then able to test whether the offspring's immune problems contribute to their autism-related behaviors. In a revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like behavioral impairments.

The researchers emphasize that because the work was conducted in mice, the results cannot be readily extrapolated to humans, and they certainly do not suggest that bone-marrow transplants should be considered as a treatment for autism. They also have yet to establish whether it was the infusion of stem cells or the bone-marrow transplant procedure itself—complete with irradiation—that corrected the behaviors.

However, Patterson says, the results do suggest that immune irregularities in children could be an important target for innovative immune manipulations in addressing the behaviors associated with autism spectrum disorder. By correcting these immune problems, he says, it might be possible to ameliorate some of the classic developmental delays seen in autism.

In future studies, the researchers plan to examine the effects of highly targeted anti-inflammatory treatments on mice that display autism-related behaviors and immune changes. They are also interested in considering the gastrointestinal (GI) bacteria, or microbiota, of such mice. Coauthor Sarkis Mazmanian, a professor of biology at Caltech, has shown that gut bacteria are intimately tied to the function of the immune system. He and Patterson are investigating whether changes to the microbiota of these mice might also influence their autism-related behaviors.

Explore further: Autism may be linked to abnormal immune system characteristics and novel protein fragment

Related Stories

Autism may be linked to abnormal immune system characteristics and novel protein fragment

January 3, 2012
Immune system abnormalities that mimic those seen with autism spectrum disorders have been linked to the amyloid precursor protein (APP), reports a research team from the University of South Florida's Department of Psychiatry ...

Recommended for you

Tackling bullying could help reduce depression in autistic teens

June 19, 2018
Teenagers with difficulties in social communication, including autism have higher rates of depressive symptoms, especially if they are being bullied.

Link found between neurotransmitter imbalance, brain connectivity in those with autism

June 6, 2018
One in 59 children in the United States lives with a form of autism spectrum disorder, according to the Centers for Disease Control and Prevention. The signs of autism begin in early childhood and can affect individuals differently. ...

Mobile app for autism screening yields useful data

June 1, 2018
A Duke study of an iPhone app to screen young children for signs of autism has found that the app is easy to use, welcomed by caregivers and good at producing reliable scientific data.

Baby teeth give clues to autism's origins, detection

May 30, 2018
A close examination of baby teeth is giving new insight into the roots of autism—and ways to spot it early.

Screening may miss signs of autism, especially in girls: study

May 21, 2018
(HealthDay)—An important checklist used to screen for autism can miss subtle clues in some children, delaying their eventual diagnosis.

Autism is not linked to eating fish in pregnacy

May 21, 2018
A major study examining the fish-eating habits of pregnant women has found that they are not linked to autism or autistic traits in their children.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.