Caltech_autism_immune_1

Study: Immune system has role in autism

CALTECH (US) — Specific changes in an overactive immune system can  indeed contribute to autism-like behaviors in mice, new research shows.

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 immune system can indeed 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.

The results appear in a paper this week in the Proceedings of the National Academy of Sciences (PNAS).

“We have long suspected that the immune system plays a role in the development of autism spectrum disorder,” says Paul Patterson, a professor of biological sciences 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 epidemiological studies—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 mouse model established, the group was then able to test whether the offspring’s immune problems contribute to their autism-related behaviors. In the most 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.

The work was supported by an Autism Speaks Weatherstone Fellowship, National Institutes of Health Graduate Training Grants, a Weston Havens Foundation grant, a Gregory O. and Jennifer W. Johnson Caltech Innovation Fellowship, a Caltech Innovation grant, and a Congressionally Directed Medical Research Program Idea Development Award.

More news from Caltech: http://media.caltech.edu/

chat7 Comments

You are free to share this article under the Creative Commons Attribution-NoDerivs 3.0 Unported license.

7 Comments

  1. Noreen Albright

    Please keep listening to the Parents of healthy children who regressed into Autism. Also, do studies on Flu shots to pregnant women. It should be against the LAW to recommend this!!!! I almost lost my baby because of it and he’s the one child with Autism. Please continue doing the “real studies’ that need to be done for PREVENTION. These numbers are Man made for sure!

  2. Nicole

    It’s interesting I had a flu when I was pregnant just before birth and my son was born with the flu and had a temperature at birth and all the first day with flu like symptoms for the first week after birth

  3. Heather

    I agree with Noreen. Just think how many pregnant women get injected with the flu shot during the first trimester of their pregnancy!! And the flu shot for pregnant women has been pushed more in recent years than ever before.

  4. Paul Patterson

    For discussion of maternal flu vaccination and more on immune connections in autism, schizophrenia and depression, check my book: http://mitpress.mit.edu/catalog/item/default.asp?ttype=2&tid=12756

    and the associated blog: http://infectiousbehavior.wordpress.com/

  5. Rana

    when my daughter was injected with vaccines as a baby she had a strange reaction, I felt like her personality changed, she went from sweet and comfortable to needy and intense. i immediately decided none of us were getting vaccines ever again.

  6. Autism spectrum

    In the resent survey it has been found that 3 out of 10 children are suffering from autism. The most common reason for autism that has come up is heredity. There is no single cause of autism but it is generally accepted that it is caused because of the disorder in brain structure. According to the recent test done on autism it has been found that Autism occur more frequently than expected among individuals who have certain medical conditions or other health related issues.

  7. Autism Parent

    My son is 29 months old and is Autistic. He has had Roseola 4 times and is sensitive to gluten and dairy. He started losing communication skills at 12 months with his first Roseola infection (not related to vaccines). He completely regressed at 15 months when he got his MMR which made matters worse. He has since had random Roseola/Measles-like rashes, puffy eyes, random fevers, etc. We have a strong family history of auto-immune disorders and “gut disorders”. We believe he was born genetically immuno-compromised and “weaker” than most children. We are getting treatment through a Naturopath/DAN! doctor and doing diet modification therapy, as well as immune system support, allergy testing, immune titer testing, and seeing results! It has everything to do with the immune system response and the digestive system. A large percentage of nervous system receptors are in the digestive system and if the digestive system becomes ill, it has a direct effect on the brain. I personally believe traditional medicine has miscategorized Autism as a behavioral disorder when does in fact have a biological origin. I am a parent who has worked in healthcare for 12 years. I am not a doctor but have done hours of reading and discussed with doctors. Our pediatrician states we just “got lucky” in finding something that works but I don’t think so.

We respect your privacy.