New research strengthens evidence that certain immune irregularities contribute to autism. The researchers found that mimicking a maternal infection in mice during pregnancy produced offspring with both lasting immune abnormalities and autism-like behaviors.
The study appears this week in the Proceedings of the National Academy of Sciences. The lead author is Elaine Hsiao, whose research is supported through her Autism Speaks Dennis Weatherstone Pre-Doctoral Fellowship grant. This fellowship program, established with a generous donation from the Stavros Niarchos Foundation, launches talented young scientists into the field of autism research.
Hsiao has been using mice to study how a mother’s infection during pregnancy may increase the risk of autism in her offspring, under the guidance of Paul Patterson, Ph.D., of the California Institute of Technology.
"We have long suspected that the immune system plays a role in the development of autism spectrum disorder," says Dr. Patterson. Several studies of brain tissue or blood samples have found links between autism and immune irregularities. In addition, several studies looking at large groups of women have linked increased risk of autism to maternal infection early in pregnancy. (Infections provoke inflammation, a strong immune response.) What remained unanswered was whether such immune changes contribute to the development of autism or stem from it.
For answers, Hsiao and her colleagues injected pregnant mice with a molecule that triggers inflammation similar to that produced by a viral infection. The offspring showed all three symptoms of autism – repetitive behaviors, decreased sociability and impaired communication.
The researchers also found immune abnormalities in the affected offspring. These included over-responsiveness in certain immune cells and decreases in other types of immune cells. These findings support those from previous studies in both animals and people.
"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. This suggests that a mother’s viral infection during pregnancy may result in lasting immune irregularities in her offspring.
The researchers also tested whether the changes in the offspring's immune system contributed to their autism-related behaviors. They gave the affected mice a bone-marrow transplant from typical mice. The normal stem cells from the transplants replenished the immune system of the animals. In addition, the treated mice no longer showed many of their previous autism-like behaviors.
“Researchers have studied immune changes in the pregnant mother or those in offspring, but rarely link the two findings together,” says Alycia Halladay, Ph.D., Autism Speaks director of research for environmental sciences. “This study is an important contribution to understanding the link between gestational immune dysfunction and outcomes.”
The Caltech researchers emphasize that results from their work in mice can't be generalized to humans. The bone marrow transplant, for example, proved useful for studying immune system changes. But this does not suggest that such transplants are a potential treatment for autism.
The results do suggest that normalizing immune irregularities could be an important target for future treatments, Dr. Patterson says. By correcting immune problems through safe and proven methods, he says, it might be possible to relieve some of autism’s classic developmental delays.
“We hope to build on this research to identify targets for effective therapies and even methods for prevention of autism and its associated medical conditions,” Hsiao adds. To do so, Hsiao plans to examine the effects of anti-inflammatory treatments on mice that display autism-related behaviors and immune changes.
Read more about Hsiao and her research in the blog she penned last year. Explore more of Autism Speaks career-launching Dennis Weatherstone Fellowship projects here. Autism Speaks is currently funding a number of studies on the immune system’s role in autism. You can explore these and other studies using this website’s Grant Search.