Research from the MIND Institute Focuses on Maternal Autoantibody-Related Autism
One of the immune system’s most critical functions is to distinguish between organisms that are self and non-self. If this determination process malfunctions, the body may form proteins called autoantibodies. In simple terms, autoantibodies are antibodies that attack the body’s own tissues, cells, or cell components, leading to a state called autoimmunity. The presence of autoantibodies can lead to or cause several types of autoimmune diseases. Previously, immune system dysfunction, autoantibodies, and autoimmune diseases have been implicated in the development of autism.
As frequently reported, autism is a spectrum disorder with a wide range of characteristics with different intensities and causes. Often, types or subtypes of autism are discussed within medical literature. One kind of autism that has received recent attention is called maternal autoantibody-related autism spectrum disorder (MAR ASD). This type of autism is identified by the presence of specific maternal autoantibodies (IgG) that react to certain proteins found in the fetal brain. These maternal antibodies can cross the placenta and access the developing brain. Once in the brain, these IgG autoantibodies may cause changes in brain development resulting in autistic behaviors in offspring.
Now, two new UC Davis MIND Institute studies have explored the current understanding of MAR ASD. The first MIND Institute study, led by Judy Van de Water and colleagues, showed that autoantibody binding to nine specific combinations of proteins (known as MAR ASD patterns) successfully predicted autism in previously diagnosed children. This study’s design involved screening the plasma of over 1000 pregnant women, including 540 mothers of children with autism, 184 mothers of kids with intellectual disability but no autism, and 420 general population mothers of children without either diagnosis. Van de Water and her team gained access to the pregnant mother’s plasma through the Early Markers of Autism (EMA) study. Their research ultimately discovered reactivity to at least one of the nine MAR ASD patterns in 10% of the group with autism, compared with 4% of the intellectual disability cohort and 1% of the general population group. Four patterns were present only in mothers whose children were later diagnosed with ASD, showing those particular autoantibody patterns to be highly predictive.
Van de Water’s work also found that a mother with reactivity to any of the nine MAR ASD patterns has approximately eight times the chance of having a child with autism. Several MAR ASD patterns were strongly linked to autism with intellectual disability. At the same time, other patterns were linked to autism without intellectual disability. The protein pattern most strongly associated with autism was (CRMP1 + CRMP2). This pattern increased the risk of autism by 16 times and was not found in the non-autism groups.
Interestingly, the second MIND Institute MAR ASD study involved geographical locations. All previous research on the topic was conducted in California and not studied in any other state until Kathleen Angkustsiri and her colleagues examined MAR ASD in two new clinical sites: the Children’s Hospital of Philadelphia (CHOP) and Arkansas Children’s Hospital and Research Institute (ACHRI). This study recruited 68 mothers of children with autism ages 2-12. These mothers provided blood samples and answered behavioral questionnaires about their children. The study also used data from the children’s clinical diagnostic assessments, including the autism diagnostic observation schedule and Social Communication Questionnaire. Findings showed MAR ASD present in 21% of CHOP’s and 26% of ACHRI’s samples. Overall, 23.5% of the mother’s blood samples were considered MAR positive, exhibiting autoantibodies reacting to known MAR ASD protein patterns. These findings are remarkably consistent with previous MIND Institute research that demonstrated the MAR subtype of autism present in 20% of a Northern California sample of children with autism.
Lead author Angkustsiri explains the importance of her research and states, “Our study showed similar MAR ASD frequencies in two other states similar to what we observed in Northern California. This suggests that the prevalence of MAR ASD is consistent across different demographics and geographic settings.”
Angkustsiri and her team’s research also examined the link between MAR ASD and autism severity. They discovered that children of mothers with +MAR antibodies had higher autism severity scores than those of -MAR mothers. However, they did not find significant differences in IQ, adaptive function, or unusual behavior.
In the end, the MIND Institute believes that further research is required to understand why mothers develop these antibodies. The institute also desires to discover how long these antibodies persist. Creating a test for MAR ASD patterns that can assess the probability of a child developing autism before characteristics and behaviors are present is the goal of both research teams. The lead authors hope that someday their research will lead to the development of an accurate clinical test to provide clinicians with more tools for an earlier diagnosis of the disorder.
