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

Autism might be better detected using new two-minute questionnaire

February 5, 2018
Researchers at Rutgers New Jersey Medical School have developed a two-minute questionnaire for parents that could help pediatricians and other primary care providers detect autism in toddlers, at a time when intervention ...

Research compares neural activity in children with and without autism spectrum disorder

January 29, 2018
Pick a hand, any hand. That familiar refrain, repeated in schoolyards the world over, is the basis of a simple guessing game that was recently adapted to study how and why kids with autism spectrum disorder (ASD) interact ...

Zebrafish study provides new insights into autism spectrum disorder research

January 24, 2018
Exposure to a compound used to treat migraines and seizures causes characteristics associated with autism, groundbreaking research with zebrafish has demonstrated.

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Nearly imperceptible fluctuations in movement correspond to autism diagnoses

January 17, 2018
A new study led by researchers at Indiana University and Rutgers University provides the strongest evidence yet that nearly imperceptible changes in how people move can be used to diagnose neurodevelopmental disorders, including ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

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.