Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is known to impair a child’s communication, social behavior, and contribute to the characteristic repetitive behaviors. Like many neurological impairments, ASD has many possible contributing factors to the disorder. In our studies this week during our Neurochemistry course, the paper we discussed outlined prenatal viral infections, zinc deficiency, abnormal melatonin synthesis, maternal diabetes, prenatal stress, toxins, and parental age as possible environmental factors that influence the development of autism.
The risk factor that I found particularly interesting to the story is maternal autoimmunity. This also relates to the age of the mother in children with autism because the majority of autoimmune disorders arise when someone is 30 years of age or older. Autoimmunity is an immune response of the body that attacks and destroys the body itself. A couple of examples of autoimmune disorders are type I diabetes mellitus, myasthenia gravis, and lupus. (Not all types of maternal autoimmunity will result in the development of ASD)
Why an autoimmune disorder is problematic for fetal neural development is that even maternal autoantibodies are able to cross the placental barrier. The placenta normally provides a selective barrier that allows immune factors and molecules for nutrition to transfer to the developing fetus, while restricting the passage of other potentially harmful molecules like pathogens. While it is a positive that the placenta allows the mother to give some passive immunity to the fetus during development, this same process is a negative for the baby when their mothers exhibit autoimmunity. A normal maternal IgG will provide the baby with protective immunity from the mother’s environmental exposures until it is able to have an immune response on its own. Unfortunately, auto reactive IgGs from the mother will also be cross the placental barrier, recognizing self-proteins and possibly interfere with fetal development.
Another interesting fact about fetal development is that the blood brain barrier of the fetus is not fully developed for the majority of gestation. For mothers, their own blood brain barrier is important because it normally restricts auto reactive IgG from the CNS. Since fetal protein reactive IgGs are able to cross the placental barrier during gestation, these IgGs may have access to the developing brain of the fetus that does not have the fully developed blood brain barrier to protect itself. It is therefore possible that fetal protein reactive IgGs of the mother that have access to the fetal brain could interfere with CNS development of the baby and result in neurodevelopmental disorders like autism. Several studies have reported that fetal brain reactive antibodies are more commonly found in the circulation of mothers of children with certain subsets of ASD.
Better understanding of autoimmune disorders and especially fetal brain reactive antibodies will be important for considering the mechanisms that fetal exposure to maternal autoantibodies have in the development of ASD.
Maternal Autoimmunity and Its Implications in Autism
