Monday, February 25, 2008

Autism Likely Caused By Interplay of Immune, Genetic and Environmental factors

Following is the link to an abstract of an article, Antibodies against fetal brain in sera of mothers with autistic children, published in the February issue of the Journal of Neuroimmunology
and the media release translating it into ordinary language for us mortals which implicates the mother's immune system as a possible contributing factor in causing autism.

Lead investigator Harvey Singer, M.D., director of pediatric neurology at John Hopkins Children's Center, stresses that autism is a complex condition caused by an interplay of immune, genetics and environmental factors. Further studies are needed to confirm that particular antibodies do indeed cross the placenta and cause damage to the fetal brain.

Autism's Origins: Mother's Antibody Production May Affect Fetal Brain BALTIMORE, Feb. 25

(AScribe Newswire) -- The mothers of some autistic children may have made antibodies against their fetuses' brain tissue during pregnancy that crossed the placenta and caused changes that led to autism, suggests research led by Johns Hopkins Children's Center investigators and published in the February issue of the Journal of Neuroimmunology.

The causes of autism, a disorder manifesting itself with a range of brain problems and marked by impaired social interactions, communication disorders and repetitive behaviors, remain unknown for an estimated 90 percent of children diagnosed with it. Genetic, metabolic and environmental factors have been implicated in various studies of autism, a disorder affecting 1 in 150 U.S. children, according to estimates by the Centers for Disease Control and Prevention.

"Now our research suggests that the mother's immune system may be yet another factor or a trigger in those already predisposed," says lead investigator Harvey Singer, M.D., director of pediatric neurology at Hopkins Children's.

Researchers caution that the findings needn't be cause for alarm, but should be viewed instead as a step forward in untangling the complex nature of autism.

Mostly anecdotal past evidence of immune system involvement has emerged from unusual antibody levels in some autistic children and from postmortem brain tissue studies showing immune abnormalities in areas of the brain. Antibodies are proteins the body makes in response to viruses and bacteria or sometimes mistakenly against its own tissues. Yet, the majority of children with autism have no clinical evidence of autoimmune diseases, which prompted researchers to wonder whether the antibodies transferred from mother to child during pregnancy could interfere with the fetal brain directly.

To test their hypothesis, the research team used a technique called immunoblotting (or Western blot technology), in which antibodies derived from blood samples are exposed to adult and fetal brain tissue to check whether the antibodies recognize and react against specific brain proteins.

Comparing the antibody-brain interaction in samples obtained from 100 mothers of autistic children and 100 mothers of children without autism, researchers found either stronger reactivity or more areas of reactivity between antibodies and brain proteins in about 40 percent of the samples obtained from the mothers of autistic children. Further, the presence of maternal antibodies was associated with so-called developmental regression in children, increasingly immature behaviors that are a hallmark of autism.

While the findings suggest an association between autism and the presence of fetal brain antibodies, the investigators say further studies are needed to confirm that particular antibodies do indeed cross the placenta and cause damage to the fetal brain.

"The mere fact that a pregnant woman has antibodies against the fetal brain doesn't mean she will have an autistic child," Singer says. "Autism is a complex condition and one that is likely caused by the interplay of immune, genetic and environmental factors."

Researchers are also studying the effect of maternal antibodies in pregnant mice. Preliminary results show that the offspring of mice injected with brain antibodies exhibit developmental and social behaviors consistent with autism.

Senior author on the study: Andrew W. Zimmerman, M.D., of the Center for Autism and Related Disorders at the Kennedy Krieger Institute.

Co-authors: Christina Morris and Colin Gause, both of Hopkins; Pam Gillin of the Kennedy Krieger Institute; and Stephen Crawford, Ph.D., Johns Hopkins Bloomberg School of Public Health. The study was funded by the Alliance for Autism Research.

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CONTACT: Ekaterina Pesheva, Johns Hopkins Children's Center, 410-516-4996, pager 410-283-1966,


Maya M said...

The new theory is interesting, but I have strong doubts in it, for the following reasons:
1) Antibodies against normal tissue components are more likely to accompany a destructive process than to cause it. E.g. they can be discovered following a myocardial infarction, but they haven't caused it.
2) It is difficult for me to see how the male prevalence of ASD could be accounted for by this theory.
3) The theory also predicts "inheritance" of autism exclusively from the mother, and a strong tendency for younger siblings of an autistic child to be also on the spectrum, especially if the age difference is small. As far as I know, neither prediction corresponds to epidemiological studies.
Still, it's interesting, let's wait and see.

Autism Reality NB said...

Maya Re point (2)The media release refers to an INTERPLAY of Immune, Genetic and Environmental factors. It would seem to me that the genetic factors would be capable of explaining the male prevalence.

Re Point (1) again it would seem to this simple layperson that there could be OTHER environmental processes accompanying the antibodies which in turn cause the impact on the fetal brain?

Re Point (3) did I miss that in the article or abstract or is that your interpretation? The researchers expressly referred to an INTERPLAY of immune, genetic and environmental factors. It seems to me that the immune factors are the maternal antibodies but the genetic could be from either parent or both?

If I misunderstood the article I would sincerely appreciate any correction you can provide.

Anonymous said...

Not sure how that would explain my identical twins. Their dad and older brother have Aspergers. One twin has Autism. His identical twin does not.

Thats why Autism Speaks had their research dept come out from CA to FL to research them.