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, epeshev1@jhmi.edu

autism

Autism and the Fever Effect

Is there a fever effect in children with autism? Can a fever temporarily offer some temporary improvement to autistic children? Some parents have thought they actually noticed such a beneficial effect from fever when their autistic children were young. I know in the past I thought I saw such an effect from fever with Conor but I thought it was just my imagination. Now, a study published in Pediatrics, suggests there may in fact be something to it; a fever may have a beneficial effect on autistic children.

In Behaviors Associated With Fever in Children With Autism Spectrum Disorders Laura K. Curran, Craig J. Newschaffer, Li-Ching Lee, Stephen O. Crawford, Michael V. Johnston, and Andrew W. Zimmerman studies 30 autistic children aged 2-18 during and after an episode of fever and documented improvements in behavior. The researchers found less "aberrant" behavior in terms of irritability, hyperactivity, stereotypy and inappropriate speech. The study authors are careful to point out several limitations in the study including possible information bias arising from data collection by parent reports and possible selection bias resulting from participation by a small fraction of eligible families from recruitment sources and make suggestions for reducing these possible biases in future studies. They clearly indicate that further study is needed to prove conclusively that the improvements are fever-specific effects. The study offers several possible biological mechanism explanations for the effects involving immunologic and neurobiological pathways, intracellular signaling, and synaptic plasticityL:

(1) neurobiological effects of selected proinflammatory16 and/or antiinflammatory cytokines, which have been found to be increased in cerebrospinal fluid (in the absence of fever) and postmortem brain tissue of individuals with autism17 and may be generated during different phases of responses to fever, (2) modification of neuronal and synaptic function secondary to variations in body temperature that influence neural conduction velocities or synaptic transmission,18 (3) modification of dynamic neural networks as a result of changes in cellular signal transduction and gene transcription that regulate synapse formation and function,19 (4) increased production of other stress-related proteins, such as heat-shock proteins, during fever that might modify energy consumption and mitochondrial activity,20 and (5) stimulation of the hypothalamic-pituitary-adrenal axis leading to modifications of neurotransmitter production and interaction.

The Fever Effect may or may not be confirmed in future studies but it is another interesting new development in the Autism Knowledge Revolution.

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