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Johns Hopkins Pediatric

An Immune Connection

Pediatric Neuro News
March 31, 2013

Edward Ahn, MD, Amir Dorafshar, MD

Antibodies give Carlos Pardo and Harvey Singer a common focus in their search for autism’s cause and cure.

Scientists searching for the roots of autism agree on one thing: No single factor causes it. Several decades of study link the disorder to a likely interplay of genes and subtle environmental influences. Now, recent findings from two Johns Hopkins labs suggest yet another contributor to the mix—the immune system.

Pediatric neurologist Harvey Singer and neuropathologist Carlos Pardo have taken two different approaches to explore the immune system’s role in autism, the early-surfacing neurological disorder marked by abnormal language and social skills.

Singer began with the idea that the process begins in the womb, suspecting that some pregnant women produce antibodies that work against brain proteins. The antibodies cross the placenta to enter the fetal brain, where they alter developing neural architecture and set the stage for autism. To test this, Singer’s group collected blood samples from 100 mothers of severely autistic children and 100 mothers of children without autism, checking for anti-brain antibodies. Results showed that significantly more mothers of autistic children carried certain antibodies, sometimes at higher levels.

But could the antibodies affect behavior? The researchers turned to animals for clues, injecting pregnant mice with antibodies collected from mothers of autistic children. After the mice gave birth, the scientists observed behavior of the offspring. As they matured, the young mice were more hyperactive and had behaviors akin to anxiety. As adults, they were less sociable than controls.

“Something appears to be happening in utero,” says Singer, who wants to repeat the study with a larger sample of mothers. At this stage, however, he’s careful not to draw sweeping conclusions. It may be that exposure to fetal brain antibodies may trigger autism in some cases. “But, clearly, we’re not describing everyone,” Singer says. “Kids develop autism for lots of reasons.”

Taking a different tack, Pardo’s group studied the immune activity of children and adults who have autism. Using brain tissue obtained from autopsied patients, the researchers measured levels of immune cells and other agents that spark inflammation. They also assayed immune system proteins in living patients with autism, by sampling their cerebrospinal fluid.

“In those with autism, the immune system was extremely active in every area of the central nervous system that we examined,” says Pardo. This, of course, doesn’t mean that revved-up immune systems cause the disorder, he adds. But he believes that “at least a subset of patients with autism have an immune system issue that helps create a clinical abnormality.”

For both researchers, then, the signs are real.

It’s no surprise that Singer and Pardo are both launching the next phases of their research. Singer plans to identify the fetal brain antibodies he’s found in the blood of some mothers of autistic children. Then he’ll investigate the nature of their brain targets. At the least, the work could help develop a diagnostic test to determine if a woman is producing—or could produce—the antibodies.

Pardo, for his part, has just completed a clinical trial of a drug that he hopes will dampen immune activity in the brains of patients with autism. The antibiotic, minocycline, is best known for treating a broad spectrum of infections. A growing body of research, however, suggests that minocycline also has antiinflammatory properties that can protect the nervous system. He’ll report results soon.

Illuminating autism’s cause is only a first step, says Pardo. “Our goal is to find the culprit and then find a way to control it.”

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