Researchers Explore Possible Immune Role in Autism

by Dan Gordon

April 5, 2007

PASADENA, Calif.--Scientific research has discredited the notion that vaccines can cause autism, which affects 1 in 150 children in the United States, according to the most recent estimate from the Centers for Disease Control and Prevention. But could something else related to the human immune system at least contribute to the disorder?

Twenty-six scientists from a variety of backgrounds, both immunology- and brain-related, participated in a workshop Jan. 25-26 at the California Institute of Technology to address that question. Although the best answer for the moment is a resounding “maybe,” they identified key questions and approaches for the next round of research.

Susan E. Swedo, a researcher in behavioral pediatrics at the National Institute of Mental Health, said during her presentation that evidence of an immunological link is accumulating.

“It’s conflicting, but it’s there,” Swedo said. Then she cited a question that Martin Raff, a biologist at University College London, had raised earlier.

“I think Dr. Raff asked the question of the day: Is an immune abnormality causing autism, is autism causing immune abnormalities, or is something else causing both?” she said.

The researchers spent much of the meeting tackling this question from different angles—clinical and research, pathological and genetic. Scientists shared their data and debated how research should proceed.

Among the possibilities: that a challenge to a pregnant woman’s immune system might influence the development of autism. Participants suggested several research ideas around this theme, including not only the identification of such an influence but also whether some kind of intervention might be possible after the baby’s birth.

Others proposed experiments to determine whether abnormalities in specific parts of the brain or immune system—such as microglia, immune cells that protect the central nervous system—contribute to autism.

Planners of the meeting, the first of its kind, succeeded in drawing participants from diverse specialties. Some had not worked on autism before.

“I thought that was an especially insightful addition to this meeting,” said Lisa Boulanger, an assistant professor of neurobiology at the University of California at San Diego. “Other fields are maybe more mature and have explored more options” when it comes to possible links with immunology, she said.

However, input from relative outsiders at first upset some participants whose lines of research were being critiqued, said Judy Van de Water, a professor of medicine at the University of California at Davis and a principal investigator at the Children’s Center for Environmental Health there.

“I took that as a challenge,” Van de Water said. “We have to work really hard to make sure we don’t make the same mistakes” as have occurred with research into diseases other participants have studied, such as multiple sclerosis.

Meanwhile, non-autism researchers learned a lot about the field. “I saw ways in which our work might relate to autism,” said Steven Maier, a neuroimmunologist at the University of Colorado Center for Neuroscience.

One challenge researchers face is that autism is part of a “spectrum” of disorders with various clinical profiles. Van de Water pointed out during the meeting that autism manifests in different ways and probably has multiple causes.

“It is really important to note that autism is not one disease,” Van de Water said.

The spectrum includes Asperger syndrome and “classic” autism. Other disorders, such as Rett syndrome, are considered by some researchers—but not all—to be part of the spectrum too.

A diagnosis of autism itself can mean different things. In its nonregressive form, autism causes subtle signs of impairment from birth. In regressive autism, children who have developed normally for about a year then show a loss of communication and social skills.

One hypothesis is that the regressive form of autism, which comprises anywhere from 10 to 30 percent of cases, may be a subtype of the disorder in which the immune system—perhaps via an infection after birth, for example—is involved.

Carlos Pardo, assistant professor of neurology and neuropathology at Johns Hopkins University and one of the meeting’s scientific chairmen, said afterward that the workshop provided promising leads for future research, including studies in both humans and animal models. The latter, he said, could shed light on whether inflammation or infection during brain development contributes to autism.

Participants are already meeting one of the organizers’ goals: that the researchers work together in the future. Boulanger, for example, is now studying a model of maternal immune challenges with Paul Patterson, a biologist at the California Institute of Technology.

Cure Autism Now and Autism Speaks, two organizations that promote and fund autism research, co-sponsored the meeting along with Peter Emch, whose son has autism. The two organizations have since merged.

A paper on the workshop proceedings is in the works. “This now needs to be communicated to a much broader audience,” said Sophia Colamarino, science director of Cure Autism Now and one of the meeting’s organizers. “This [meeting] was just a first step.”