Possible Link Discovered Between Immune Irregularities And Autism

The question of what causes Autism, a neural development disorder, has been an ongoing debate for years upon years, with research proving and disproving one thing or another.  Are children born with it?  Is it genetic?  Were they exposed to toxins?  Did their vaccinations attribute to it?  Unfortunately, the debate continues to rage.

Although there may be no current absolute answer, researchers have not given up on figuring out this devastating disorder.

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The latest research to come from the Scientists at the California Institute of Technology, Caltech, has possibly discovered a link between the immune system and the disorder that is characterized by social-interaction difficulties, communication challenges and a tendency to engage in repetitive behaviors.

The 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.

“We have long suspected that the immune system plays a role in the development of autism spectrum disorder,” says Paul Patterson, the Anne P. and Benjamin F. Biaggini 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.”

They first established 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.

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The team found that the offspring exhibited the core behavioral symptoms associated with autism spectrum disorder.  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 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.

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These results appeared in a paper in the Proceedings of the National Academy of Sciences (PNAS).

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