By Roberta Attanasio
The world of autism is a diverse one — autism and autism spectrum disorder are general terms for a group of complex and extremely heterogenous life-long neurodevelopmental conditions. Autism is also one of medicine’s greatest challenges. The current general consensus is that autism has multiple causes, and these causes can be as varied as the types of autism, which are not very well defined, yet. It is almost certain, though, that autism has its roots in very early brain development, development that can be influenced by a variety of factors.
In a subset of childrem with autism, one of these factors may involve production of antibodies by the mother — not the antibodies that defend us from infection — rather, antibodies that bind our own molecules and therefore may lead to damage of our own cells. These antibodies are called auto-antibodies and, in the case of some autistic children, may induce damage of brain cells.
During pregnancy, maternal antibodies are normally transferred to the fetus through the placenta to protect the infant from infection. However, the same placental transfer system can also allow auto-antibodies to reach the fetus — indeed, the placental transfer system does not discriminate between “good” and “bad” antibodies. If, before or during pregnancy, the mother produces auto-antibodies that bind the fetal brain, and these auto-antibodies reach the fetal brain, normal brain development can be hindered.
Results from a recent study (July 2013) by Judy Van de Water (UC Davis MIND Institute) and collaborators show that mothers of children with autism produce auto-antibodies that bind seven proteins involved in different aspects of brain development. These proteins are found throughout the body and are present at significant levels in the human fetal brain, where they play established roles in neurodevelopment.
The study, entitled “Autism-specific maternal autoantibodies recognize critical proteins in developing brain” and published in the scientific journal Translational Psychiatry, involved 246 mothers with children affected by autism and 149 mothers with normally developing children. Twenty-three percent of the mothers with children affected by autism produced auto-antibodies that recognized two or more of the seven proteins, whereas only 1 percent of the mothers with normally developing children produced such auto-antibodies.
The investigators coined a special designation for the type of autism possibly linked to these auto-antibodies — maternal autoantibody-related (MAR) autism. Van de Water said “It is important to note that women have no control over whether or not they develop these autoantibodies, much like any other autoimmune disorder and, like other autoimmune disorders, we do not know what the initial trigger is that leads to their production.”
The autoantibody/MAR hypothesis appears to be supported by a variety of studies carried out in animals during the past few years. For example, results from a study published in 2009 show that antibodies collected from mothers of children with autism and experimentally transferred to pregnant mice produce neurobehavioral alterations in the offspring.
This hypothesis applies to only a subset of children with autism spectrum disorder. A few months ago, a study pointed out a possible link between autism and air pollution. Indeed, there are multiple genetic and environmental factors currently under study.
For children affected by MAR autism, the identification of specific brain proteins representing the target of maternal autoantibodies may represents a much-needed pathway to treatment. Finding out why women produce auto-antibodies against proteins present at significant levels in the fetal brain will provide another much-needed pathway, the pathway to prevention.