Immunologists from UC Davis M.I.N.D. Institute find clear biological component to perplexing childhood neurological disorder
A new study by researchers at the University of California, Davis, M.I.N.D. Institute and the NIEHS Center for Children’s Environmental Health demonstrate that children with autism have different immune system responses than children who do not have the disorder. This is important evidence that autism, currently defined primarily by distinct behaviors, may potentially be defined by distinct biologic changes as well.
“Understanding the biology of autism is crucial to developing better
ways to diagnose and treat it,” said Judy Van de Water, associate professor
of rheumatology, allergy and clinical immunology at the UC Davis School of
Medicine and the UC Davis M.I.N.D. Institute. “While impaired communication
and social skills are the hallmarks of the disorder, there has not yet been
strong scientific evidence that the immune system is implicated as well. We
now need to design carefully controlled studies that tell us even more about
the way in which a dysfunctional immune system may or may not play a role in the disorder itself.”
Van de Water, along with co-investigator of the study Paul Ashwood,
assistant professor of medical microbiology and immunology at the UC Davis
M.I.N.D. Institute, isolated immune cells from blood samples taken from 30
children with autism and 26 typically developing children aged between two
and five years of age. The cells from both groups were then exposed to
bacterial and viral agents that usually provoke T-cells, B cells and
macrophages – primary players in the immune system.
Of the agents tested in the study – tetanus toxoid, lippopolysaccharide derived from E. coli cell walls, a plant lectin known as PHA, and a preparation of the measles, mumps and rubella vaccine antigens – the researchers found clear differences in cellular responses between patients and controls following exposure to the bacterial agents and PHA.
In response to bacteria, the researchers saw lower levels of protein
molecules called cytokines in the group with autism. Cytokines function as
mediators of the immune response, carrying messages between B, T and other immune cells. They also are known to be capable of having profound effects on the central nervous system, including sleep and the fever response.
Immune system responses to PHA, in contrast, produced more varied cytokine levels: Higher levels of certain cytokines and lower levels of others.
According to Van de Water and Ashwood, these studies illustrate that under
similar circumstances, the cytokine responses elicited by the T-cells,
B-cells, and macrophage cell populations following their activation differs
markedly in children with autism compared to age-matched children in the
general population. Cytokines are known to affect mood and behavior, and
while their specific role in the development of autism remains unclear, the
potential connection is an intriguing area of research that warrants further
investigation.
“This study is part of a larger effort to learn how changes in immune
system response may make some children more susceptible to the harmful
effects of environmental agents,” said Kenneth Olden, director of the
National Institute of Environmental Health Sciences, the federal agency that
provided funding for the study. “A better understanding of the connection
between altered immune response and autism may lead to significant advances in the early detection, prevention and treatment of this complex
neurological disorder.”
“We would like to take these findings and explore whether, for
example, the cytokine differences are specific to certain subsets of
patients with autism, such as those with early onset, or those who exhibit
signs of autism later during development,” Ashwood said. He added that the
logical next step is to look directly at specific cell populations that may
be responsible for the diverging responses between patients and controls.
This study was supported by grants from the National Institutes of
Environmental Health Sciences, the U.S. Environmental Protection Agency, the
UC Davis M.I.N.D. Institute, Ted Lindsay Foundation and Visceral. The UC
Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders)
Institute is a unique collaborative center for research into the causes and
treatments of autism, bringing together parents, scientists, clinicians and
educators.
For further information, go to http://www.ucdmc.ucdavis.edu/mindinstitute