Maternal Autoantibodies May Increase Autism Risk

Date: 
January 16, 2008

A new study has found that women with certain antibodies in their blood may be at an increased risk for having children with autism. Researchers hypothesize that these antibodies may disrupt fetal brain development in utero by mistakenly targeting fetal brain tissue. The study, led by Judy Van de Water, Ph.D., at the University of California at Davis, was published in the journal Neurotoxicology.

Normally antibodies help us fight off infection, and this beneficial role extends into pregnancy, where a mother's antibodies pass to her developing fetus. But in some cases, antibodies can turn against us, targeting our own tissues instead of pathogens; these renegade "autoantibodies" cause autoimmune diseases like lupus or multiple sclerosis. "My background is in autoimmunity and thus I was aware of the role of maternal autoantibodies in the pathology of certain disorders in the children born under these conditions," Dr. Van de Water said via email. "We surmised that as antibodies cross the placenta, there would be a possibility that maternal antibodies against fetal brain could play a role in autism."

The new study found antibodies in mothers' blood that targeted two specific proteins in fetal brain tissue. Seven out of 61 mothers of children with autism had antibodies to both proteins, whereas none of the mothers of developmentally-delayed or typically-developing children had both antibodies. Having only one of the antibodies was also associated with autism: mothers with the antibody to the smaller protein were over five times more likely to have a child with autism. Interestingly, having both antibodies was more associated with the regressive form of autism.

While the presence of these antibodies was linked to autism, it is important to note that they were not exclusively found in mothers with autistic children. Some mothers with typically-developing children had one or the other of these fetal brain-binding antibodies, although to a lesser extent than those with autistic children, and in no case did they have both types. Likewise, many mothers of autistic children did not have these antibodies, perhaps related to the likelihood of multiple causes for autism.

Future research will explore the potential role of these autoantibodies in the development of autism. "We are currently pursuing the identity of these autoantigens," said Dr. Van de Water, referring to the two brain proteins targeted by the antibodies. To support immediate continuation of this research, Dr. Van de Water has just received an Autism Speaks' Mentor-Based Fellowship grant. (read more here)

It will also be important to establish whether these antibodies are actually present during pregnancies that result in a child who develops autism: in this study, the antibodies were found in mothers several years after the pregnancies of their affected children. To address this, a prospective study is currently underway to find out whether mothers with these antibodies during pregnancy go on to bear children who eventually develop autism. This study is currently recruiting mothers of children with autism who are considering having another child and who live in northern California. If you are interested in participating, more information can be found at http://marbles.ucdavis.edu.

Connections between the immune system and autism have also been reported in two recent studies funded by Autism Speaks. Unlike the mother-focused study described above, these studies looked at children with autism for immune system abnormalities. Led by Paul Ashwood, Ph.D., also at UC Davis, scientists found that levels of an immune signaling protein called interleukin-23 (IL-23) was significantly different in blood samples from autistic children when compared to typically-developing children. This may ultimately impact brain inflammation because IL-23 promotes the survival of a type of lymphocyte that is involved in initiating inflammatory responses. The second study, also led by Dr. Ashwood, found that altered levels of brain-derived growth factor (BDNF) were produced by blood cells from children with autism, both at rest and in response to a simulated pathogen. Since BDNF promotes neuron survival and function, this finding suggests that immune responses could modulate neural function via the BDNF produced by these blood cells. These studies were published in a special autism issue of the American Journal of Biochemistry and Biotechnology.

Investigations of the immune system in autism by these scientists and others will discover whether factors like antibodies and interleukins, perhaps in combination with genetic susceptibility, may influence brain development in a way that can lead to autism. These findings show how critical it is to pursue every research avenue, even unexpected ones like the immune system, to bring us closer to answers about autism.

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