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Monday 15th November, 2004
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Researchers found that brain tissue from 11 people with autism
showed signs of immune system activation.
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Inflammation in the brain is clearly a feature of autism,
according to a new study published November 15, 2004, in
online edition of Annals of Neurology, the scientific
journal of the American Neurological Association. The
researchers found strong evidence that certain immune system
components that promote inflammation are consistently
activated in people with autism.
"These findings reinforce the theory that immune activation in
the brain is involved in autism, although it is not yet clear
whether it is destructive or beneficial, or both, to the developing
brain," said senior author Carlos A. Pardo-Villamizar, M.D., at the
Johns Hopkins University School of Medicine in Baltimore, Maryland.
Autism is a disorder of the developing brain that appears in
early childhood. It is estimated to afflict between 2 and 5 of every
1000 children and is four times more likely to strike boys than
girls. Children with autism have difficulties in social interaction
and communication and may show repetitive behaviors and have unusual
attachments to objects or routines.
Autism has a strong genetic component, and in some families,
autism tends to be more prevalent. In identical twins with autism
both are usually affected. However, the number of children with
autism appears to be increasing more than expected for a genetic
disorder. This suggests to scientists that genetic abnormalities
require the influence of other factors to cause the disorder. Birth
complications, toxins, diet, and viruses and other pathogens have
been suggested, though there is no strong evidence for any of these.
In recent years, there have been scientific hints of immune
system irregularities in children with autism, but not all studies
have confirmed this. Pardo and his colleagues sought a more
definitive answer by looking not at the immune system overall, but
at immune components inside the relatively sealed environment of the
nervous system.
Led by first author Diana L. Vargas, MD, a post-doctoral fellow
working in Pardo's laboratory, the researchers examined brain tissue
from 11 people with autism, aged 5 to 44 years, who had died of
accidents or injuries. Compared with normal control brains, the brains of the people
with autism featured immune system activation and inflammation in
the brain. "This ongoing inflammatory process was present in different areas
of the brain and produced by cells known as microglia and astroglia,"
said Pardo.
When the researchers measured brain levels of immune system
proteins called cytokines and chemokines, they found abnormal
patterns consistent with inflammation. "The pattern of cellular and protein findings indicate that they
are part of the 'innate' immune system in the brain, and do not
appear to be caused by immune abnormalities from outside the brain,"
said Pardo.
The findings in the brain tissue were corroborated by studies of
cerebrospinal fluid obtained from six children with autism (ages 5
to 12 years), in which cytokines that promote inflammation were
found to be elevated. It is conceivable that signs of inflammation in the cerebrospinal
fluid could one day be used to diagnose autism, or even that doctors
could treat inflammation to prevent or combat autism, however this
is still speculative, according to Andrew W. Zimmerman, a pediatric
neurologist at the Kennedy-Krieger Institute in Baltimore and
co-author of the paper. For one thing, it is possible that the
inflammation represents the brain's efforts to combat some other
process damaging to brain cells.
"These findings open new possibilities for understanding the
dynamic changes that occur in the brain of autistic patients during
childhood and adulthood. Although they may lend themselves to
development of new medical treatments for autism, much more research
would be needed to establish the validity of this approach," said
Pardo.
"Currently, there are no biological tests that support
the diagnosis of autism", says Dr. Heba Ismail from The Doctors
Lounge. "One would hope that the possible detection of signs of
inflammation in the brain or cerebrospinal fluid could one day be
used for the earlier diagnosis of autism, and therefore earlier
intervention plans."
Among the next steps in this line of research, Pardo and
colleagues are studying how the genetic background of patients and
families may influence the development of immunological reactions in
the brain that confer susceptibility to autism.
Sources
Article: "Neuroglial Activation and Neuroinflammation in the Brain
of Patients with Autism," Diana L. Vargas, Caterina Nascimbene,
Chitra Krishnan, Andrew W. Zimmerman, and Carlos A. Pardo; Annals of
Neurology; Published Online: November 15, 2004 (DOI:
10.1002/ana.20315).
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