"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.
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.
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).
The Annals of Neurology, the preeminent neurological journal worldwide, is published by the American Neurological Association, the world's oldest and most prestigious neurological association. The 1,400 members of the ANA--selected from among the most respected academic neurologists and neuroscientists in North America and other countries--are devoted to furthering the understanding and treatment of nervous system disorders. For more information, visit www.aneuroa.org.
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Annals of Neurology