Often when we think about our immune system we think of it helping us survive and fight off disease, but rarely, unless it affects us directly, do we think of our immune system harming us. When this happens, it is called an autoimmune disease. This is when a person’s immune system has a response against self-antigens involving T-cells, B-cells, or autoantibodies, all of which are specialized immune cells in our bodies.
This immune response can cause systematic injury or attack a specific organ system, resulting in diseases such as rheumatoid arthritis, lupus, or inflammatory bowel arthritis. I wouldn’t be surprised if a lot of people had no idea that these are autoimmune diseases.
These autoimmune diseases are more prevalent than we might think, though. According to the Centers for Disease Control and Prevention, autoimmune diseases are the third most common category of disease behind heart disease and cancer, affecting about 8% of our population (22 million people), maybe many more in a minor capacity. More than 75% of these people are women.
Because of this, it is extremely important that researchers have linked autoimmune diseases and immune dysfunction to Autism Spectrum Disorder (ASD). Research has shown since the 1950s that autoantibodies produced by a pregnant woman with an autoimmune disease can harm the neurodevelopment of the embryo. More recently, though, this hindrance of neurodevelopment has been shown to cause ASD.
The autoantibodies mentioned above are specialized antibodies (proteins that are produced by the cells of the immune system to identify and neutralize pathogens) that are directed against the individual’s own cells. The production of these autoantibodies is the cause of many autoimmune diseases, and the fact that they attack the individual’s own cells is what causes many of the symptoms associated with the disease. In the case of ASD specific autoantibodies, anti-brain autoantibodies, are thought to cause ASD because they attack proteins and cells in the brain of the developing embryo. They have been shown to attack proteins such as lactate dehydrogenase A (LDH-A) and B (LDH-B), stress-induced phosphoprotein 1 (STIP1), guanine deaminase, collapsin response mediator proteins 1 (CRMP1) and 2 (CRMP2), Y-box binding protein 1, and others (Figure 1), all of which have important roles in neurodevelopment.
A study published in 2009 studied the prevalence of ASD in 700,000 children born in Denmark, finding that type 1 diabetes, rheumatoid arthritis, and celiac disease (all of which are autoimmune diseases) correspond to increase risk of ASD. Another study showed that maternal autoimmune diseases were linked to a 34% increase in risk for developing ASD.
The antigens recognized by maternal autoantigens are significant because several of the targets of the autoantigens are critical for normal brain development, specifically processes essential for neuronal migration and neural network formation. The studies that show links between maternal autoantibodies and ASD were performed in humans, so the mechanism of how these autoantibodies cause ASD is still not completely understood. Animal models are currently being studied intensely to hopefully discover the etiology of ASD in relation to immune dysfunction.
Murine and primate models have been used to study the clinical significance of maternal autoantibodies to show that they are not just correlative. To do so, primate mothers were injected with IgG, an autoantibody, and their offspring were studied. Social behaviors in these offspring were different than normal primates and stereotypical of patients with ASD. Similar studies were carried out in mice and the findings were similar to those found in the primate studies ().
Other research groups have also linked the presence of anti-brain autoantibodies to other behavioral disorders such as schizophrenia, Tourette syndrome, and obsessive compulsive disorder. Unlike the autoantibodies found in the brains of individuals with these diseases, the autoantibodies found in the brains of patients with ASD have been shown to preferentially bind to fetal targets instead of adult targets, which could be the reason that they hinder neurodevelopment in the way that they do.
There is still much unknown about autoantibodies, but researchers hope that by discovering the mechanism by which autoantibodies hinder neurodevelopment they will be able to implement therapeutic interventions that could prevent ASD and other neurodevelopmental or psychiatric disorders.
Our Immune Systems and Autism Spectrum Disorder
