Wednesday, November 29, 2006

Autism Spectrum Disorder & immune system

SAN FRANCISCO, CA, United States (UPI) -- Scientists trying to dig up the roots of autism are unearthing mounting evidence of the immune system`s involvement in the intractable disorder.
Scientific hints that the body`s disease-fighting mechanisms play a role in autism first surfaced in 1986, researchers said.
However, for the most part, these studies were small and the results inconclusive so that what now appears a logical concept didn`t catch on until more recently, said David Amaral, professor of psychiatry and behavioral sciences at the University of California, Davis, School of Medicine and Medical Center and M.I.N.D. research director.
'You cannot have a normal neurodevelopment without having a normal immune system,' said Judy Van de Water, an immunology specialist at the UC Davis Center for Children`s Environmental Health.
'We know when these kids are faced with particular environmental agents, such as certain bacteria, they don`t respond as rigorously as the control kids do.'
Among other projects, she`s looking into whether children with autism show signs of autoimmunity, a phenomenon in which the body`s protective system goes haywire, turning on the very tissues and organs it`s supposed to safeguard from attack.
'This is important because a lot of investigators have suggested that patients with autism have auto-antibodies, so we`re looking at whether these kids have auto-antibodies to brain tissue,' she told an international meeting on autism research in Boston.
Indeed, when Van de Water probed the brain`s disease-deflecting armor in 30 autistic children ages 2 to 5 and 26 without the disorder, she detected a variation in the way specialized messenger molecules called cytokines react to bacteria and other health threats in the two groups.
These immune proteins, which normally get into gear when a response is needed to injury or irritation, instead appear to be constantly 'switched on,' or inflamed, in individuals with autism, reported another team, which veered off the beaten path to study the issue.
Rather than taking the more common approach of looking at the immensely complex immune system as a whole, the investigators from Johns Hopkins University School of Medicine in Baltimore and the University of Milan in Italy decided to narrow their field of inquiry to just a few components within the relatively restricted environment of the central nervous apparatus.
They confined their search to the cell-coordinating cytokines, measuring their levels in brain tissue samples taken from 11 children and adults ages 5 to 44 who had died by accident, illness or injury.
They observed the abnormal patterns of inflammation, reinforcing the view that immune activation in the brain is involved in autism. However, the authors noted, it is not yet clear whether the irregularity is destructive or beneficial, or perhaps both, to the developing brain.
Wanting to see if their findings would hold up, the investigators followed up with an analysis of cerebrospinal fluid from six children with autism ages 5 to 12.
As in the previous studies, they once again detected elevated cytokine levels, raising the possibility that ultimately doctors might be able to use these anomalies to diagnose autism or even that they might be able to treat the inflammation, thereby preventing or reversing the disorder.
But that`s a long time and many studies away.
First, they must deal with such challenges as figuring out the chicken-and-egg quandary that can sabotage attempts to definitively get at the source of an ailment.
In the case at hand, the scientists were uncertain whether the abnormality they observed is a cause or consequence of the disorder.
Just as the body`s first-aid response to a skinned knee is to protectively wall off the injury and ward off the agent of harm with heat, redness and swelling, so, too, it may be that the inflammation detected by the researchers may represent the brain`s efforts to combat some other cell-damaging process.
The finding 'backs up what we`re seeing in the peripheral blood, that perhaps there is a change in these kids and the cytokine production in the brain is altered,' said Van de Water, who plans to conduct her own investigation into what those changes mean, whether they affect brain function and how they might be related to some of the classic symptoms of autism.
For example, cytokines are known to affect slumber, and sleep disorders are a common complaint of individuals with autism.
Among the next steps, scientists are looking into what role heredity may play in the development of immune abnormalities in the brain that may stir up a susceptibility to autism.
To get a clue, Van de Water and other researchers are looking back, sifting through tens of thousands of medical histories for any patterns in the rates of earaches, colds and other infections in autistic youngsters.
Although still preliminary, results of one study -- of 88,000 babies born between 1995 and 1999 in Northern California -- hint at an increased risk of autism in the offspring of mothers with psoriasis, a chronic condition that runs in families.
Some 3 million American women of child-bearing age have the disorder marked by itchy, scaly, inflamed skin on the elbows, knees, back and/or scalp, according to the patient advocacy group Psoriasis Cure Now!
The early findings also indicate expectant mothers suffering from asthma and allergies -- particularly during the second trimester -- may face double the typical risk of giving birth to a child with autism.
However, the presence during pregnancy of 45 other autoimmune diseases that turn the body against itself -- including rheumatoid arthritis, type 1 diabetes, rheumatic fever, certain heart complications, lupus and multiple sclerosis -- appear to have no bearing on the baby`s autism status, the study authors reported.
These maladies are under scrutiny because they affect primarily women -- who account for 78 percent of all cases -- and because chemicals produced in response to their presence often are found at high levels in the bloodstream of autistic children.
That would suggest a possible link between autism and pre-birth exposure to an autoimmune ailment, scientists said.
The authors speculate a common genetic cause may underlie such conditions as asthma and autism. Or, because the mother`s illness was frequently diagnosed in the second trimester of pregnancy, the flare-up may have triggered her immune system to produce more inflammatory cytokines, which, in turn, might have disrupted brain development in the fetus, the researchers proposed.
(Note: In this multi-part installment, based on dozens of reports, conferences and interviews, Ped Med is keeping on eye on autism, taking a backward glance at its history and surrounding controversies, facing facts revealed by research and looking forward to treatment enhancements and expansions. Wasowicz is the author of the forthcoming book, 'Suffer the Child: How the American Healthcare System Is Failing Our Future,' to be published by Capital Books.)
Next: Some autism study results point in genetic directions
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