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Maternal Antibodies as a Biomarker?

Unusual findings extend the search
September 21, 2009

The foray into the intersection between autism and immunology has borne many interesting results throughout the years, the latest of which is the discovery of maternal antibodies to fetal brain proteins. Three research articles published in 2008 from two groups of researchers from University of California-Davis/MIND Institute and Kennedy Krieger Institute/Johns Hopkins University, reported the presence of "autoantibodies"
(antibodies developed against self) in the blood of mothers who had previously given birth to children with autism.

In the on-going search for biological risk-markers of autism, the two groups independently reported that abnormal antibody proteins were present more often in the blood of mothers who had given birth to children diagnosed with autism than those who had not. Both teams found that mothers whose children have specifically presented with a regressive form of autism have antibodies that bind to as-yet unidentified proteins present in fetal brains. In a third study, also from the MIND Institute, researchers found that exposing pregnant rhesus monkeys to purified antibodies isolated from the sera of mothers of children with autism resulted in offspring that developed extremely unusual stereotypic behaviors.

Maternal antibodies have been previously implicated in other conditions such as the movement disorder Myasthenia Gravis and Grave's disorder, the most common form of hyperthyroidism. In these diseases, an autoimmune condition in the mother can affect the child because antibodies directed against self proteins can cross the placenta to affect the developing fetus, likely by binding and disrupting the action of the proteins recognized by the antibody. However, the specific meaning and mechanism of action of the autoantibodies found in the mothers of children with autism is still a mystery.

Given the overarching need to find biomarkers that can help parents diagnose their risk of having a child with autism, many follow-up studies are underway to determine the significance of these maternal antibodies. Foremost among them is the identification of the actual proteins targeted by the antibodies, which would provide critical knowledge about the mechanism by which fetal brain development is disrupted. Meanwhile, these findings represent important knowledge that can be used for risk assessment in the future, particularly by women planning pregnancies. And although the correlations found apply only to a subpopulation of autism spectrum disorders, they represent a group for which an intervention can be devised when the pathological role of these antibodies is understood. A role for the immune system during brain development, and in particular, in disorders such autism, is an area of investigation that has remained far less explored than others. However, the year 2008 showed that it is an area rapidly gaining momentum and that should provide many more insights in the upcoming year

Braunschweig D, et al. Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology. 2008 Mar;29(2):226-31. Epub 2007 Nov 6.

Martin LA, et al. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008 Aug;22(6):806-16. Epub 2008 Feb 8.

Singer HS, et al. Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol. 2008 Feb;194(1-2):165-72. Epub 2008 Feb 21.