Johns Hopkins Medicine
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Nov. 15, 2004


A Johns Hopkins study has found new evidence that the brains of some people with autism show clear signs of inflammation, suggesting that the disease may be associated with activation of the brain’s immune system.   
“These findings reinforce the theory that immune response in the brain is involved in autism, although it is not yet clear whether the inflammation is a consequence of disease or a cause of it, or both,” said Carlos Pardo-Villamizar, M.D., assistant professor of neurology and pathology at Johns Hopkins and senior author of a report on the study published early on-line in the journal Annals of Neurology on Nov. 15.

Whatever the cause of the inflammation, it may provide a good target for developing new treatments, adds Pardo.

Autism is a disorder of the developing brain that appears in early childhood. According to the American Neurological Association, it is estimated to afflict between two and five of every 1,000 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 in some families, although other causes likely play a role, possibly including birth complications, diet, toxins or infections, says Pardo. 

“Scientists have found hints that the immune system may be involved in autism, but not all studies have confirmed this,” said Pardo.  “We wanted a more definitive answer, so rather than looking at the overall immune system, we focused on immune responses inside the relatively sealed environment of the nervous system.”

Led by first author Diana L. Vargas, M.D., a postdoctoral fellow working in Pardo’s laboratory, the researchers examined tissue from three different regions of the brain in 11 people with autism, ages 5 to 44 years, who had died of accidents or injuries.  They also measured levels of two immune system proteins, called cytokines and chemokines, found in the cerebrospinal fluid - the clear substance that surrounds, bathes and nourishes the brain and spinal cord - in six living patients with autism, ages 5 to 12 years.

Compared with normal control brains, the brains of people with autism showed evidence of an ongoing inflammatory process in different regions of the brain and produced by cells known as microglia and astroglia, says Pardo.  Cytokine and chemokine levels in the cerebrospinal fluid also were abnormally elevated in patients with autism.

“These findings suggest that the inflammation is localized to specific regions within the brain and not caused by immune system abnormalities from outside the brain,” says Pardo.

Pardo and colleagues are now studying how the genetic background of patients and families may influence immune system reactions in the brain associated with autism.

Other authors are Andrew Zimmerman, Caterina Nascimbene, and Chitra Krishnan.  The study was funded by the Cure Autism Now Foundation, the Autism Research Foundation, the National Institutes of Health, Dr. Barry and Renee Gordon and an anonymous donor.

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