Exciting new research over the past five years is suggesting the immune system may play a key role in the development of neurological and behavioral deficits in children with autism spectrum disorders and other developmental and learning disorders.
Autism spectrum disorders are a range neurodeveleopmental disorders characterized by social deficits and communication difficulties, stereotyped or repetitive behaviors and interests, sensory issues, and in some cases, cognitive impairments and delays. The idea that these disorders may have a genetic component to them is not new. What is becoming apparent with recent research is there is a link between a familial history of autoimmune disease and risk for autism within that family.
A study published in Pediatrics (Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders; Atladottir, Pedersen, Thorsen, Mortensen et.al. Pediatrics 2009; 124;687-694 ) in 2009 examined 3325 children diagnosed with autism spectrum disorders and studied the family histories of autoimmune disease in these children. It was determined that children with a familial history of rheumatoid arthritis or celiac disease had an increased risk for developing these disorders. It also showed an increased risk for the development of infantile autism in families with a history of juvenile diabetes. Other studies have shown similar correlations.
As autism is known to be a neurological developmental disorder, researchers have begun examining the possible role that folic acid (and its metabolism and transport within the body) may play in the development of the disorder. This makes sense on many levels. Any mother in the past few decades has be recommended a prenatal vitamin with adequate folic acid both before conception and during the pregnancy to help support proper neuronal development and to prevent neural tube defects. It seems logical that perhaps folic acid issues could be involved in autistic neuronal development deficiencies as well. While investigating this concept, they are finding even more evidence to support the idea of an immunological component to the neurodevelopmental issues in autism spectrum disorders.
They began studying how folic acid makes it's way into the brain to support neurological development in the brain. The brain is obviously a very "finely tuned" instrument and has to control it's environment extremely carefully. It has to regulate sugar in the blood stream, oxygen levels, electrolyte levels, various hormone levels, etc. It needs to be protected from the rest of the body in order to do this. This is what the blood brain barrier does. It's acts like a "filter" for anything entering the brain through the circulatory system. It will allow critical elements and compounds through to the neurological tissue (oxygen, glucose, vitamins and minerals) and will block unwanted compounds, molecules and infectious agents from passing into this tissue. The items that pass through this filter into the neurological tissue do so through various "transport systems" set up in the barrier, to "transport" the favorable compounds through. Imagine security gates set up throughout this barrier. They allow the passage of oxygen, glucose, folic acid, etc. and will block unwanted compounds and molecules.
Folic acid is one element that has to be transported through these "security gates" barrier in order to get into the neurological tissue in the brain. Autism researches hypothesized that there may be a "block" at this gate preventing the proper passage of folic acid into the brain in these children, leading to possible folic acid deficiencies and neurological deficits. The study outlined below shows the findings of this initial research.
They tested 93 autistic kids for what are called Folate Receptor Auto-antibodies (FRA's). These are antibodies produced by the child's immune system, which will bind to / react against the folate receptor in the blood brain barrier. If these antibodies bind to these receptors, they "block" the passage of folate through this security gate into the brain, thus potentially leading to a folate deficiency in the brain.
These children with elevated FRA's were then treated with extremely high doses of folic acid (50mg). 75% of these children showed marked improvements in communication, language, attention and stereotypical behavioral patterns over the 4 months of treatment. It's important to note that this studied folate acid replacement as a treatment, and did not attempt to identify and remove what was potentially causing the blockage and folate deficiency. Even without this aspect studied, the results of the studied treatment were extremely significant.
Another 2013 study attempted to identify what may have been triggering this autoimmune attack against the Folate receptors in the blood brain barrier. Over 1/3 of the children in the study had bovine casein antibodies shown to react/bind to the folate receptors in the blood brain barrier. A significant correlation between anti-casein antibodies and folate receptor binding (blocking) was found. No correlation was found in the non-autistic control group for the study.
Another cohort study published in the journal Frontiers of Human Neuroscience in 2013 determined the "..the majority of published studies indicate statistically significant positive changes to symptom presentation following dietary intervention. In particular, changes to areas of communication, attention, and hyperactivity..."
So to summarize this research in simple form...
Research has determined an increased risk for development of these neurodevelopmental disorders in children with autoimmune disease in their family histories. We know there is an immunological association.
Folate deficiencies have been identified in a significant percentage of children with autistic spectrum disorders. Supplemental folate protocols have been shown to be beneficial for a statistically significant percentage of children treated.
"Auto-antibodies" against folate receptors in the brains have been identified children with autistic spectrum disorders
These auto-antibodies have been positively correlated with levels of anti-casein antibodies in the blood stream of the affected children.
This research supports both the idea that Autism Spectrum Disorders could possibly be associated with an autoimmune reaction against the receptors that allow folic acid to get into the brain, and support proper neuronal development. If this transport is blocked, then folate deficiency could result, and this could impair proper neuronal development. The research also supports the idea of "molecular mimicry" discussed in a previous article (Can food trigger Autoimmune Disease?). In this case, a child could be fed a food that they are allergic to (produce antibodies against)and these antibodies could cross react with receptor proteins on the blood brain barrier (folate receptors) and block the transport of folic acid into the neuronal tissue, leading to developmental delays.
In this example, the food allergy doesn't directly cause the condition (ASD) but it affects another body system, causing it to function poorly over a long period of time, slowly leading to the symptoms of the condition (behavioral issues in kids with ASD). It's quite possible that there may be no other symptoms of the primary food allergy either. This child could be fed the food and have no other symptoms associated with the food allergy. If the antibodies to the food only attack the folate receptors in the brain, then it could take months to years before symptoms of delayed or impaired neuronal development (as a result of low folate in the brain) may present. There is likely going to be no way to correlate that food reaction with their condition or symptoms.
Some of the studies above showed improvements in a significant portion of the study populations. Why didn't the interventions show reactions in most or all of the kids? There are too many possible explanations for this to discuss in detail here. There are a few key obvious points that could affect these results however.
The age of the child at the time of the treatment. If an older autistic child has been suffering with his condition for some time, there could be permanent damage done to the transport mechanisms for folate to get into the brain. In this case, high dose folate supplementation may be of little help if it can't get transport into the brain tissue. If you can implement these changes while the child is still in active neuronal development, they may be able to respond to the treatment more effectively and repair some of the damage caused by the deficiency of folate during early development.
Identify and remove the dietary allergy creating the block. If you supplement a folate deficient child with high dose folic acid, but don't get rid of the blockage preventing it's absorption into the brain, you may not have positive results with the supplementation.
Identify and treat other biochemical and hormonal imbalances caused by the primary immune reaction. This is a significant part of treatment for this condition, see below.
Folic acid deficiency may be only one small part of a biochemical hormonal imbalance contributing to the child social and behavioral symptoms. If you just treat that one imbalance and don't look for and address the other possible ones, treatment response may be limited. The adrenal gland system is also directly involved in any long term immunological reaction in the body (see article on Chronic Fatigue). Long term immunological or inflammatory processes in the body ultimately lead to dysfunction in the adrenal gland system. This is your stress suppressing system. When this system gets over taxed by a chronic immune system problem, symptoms such as fatigue, anxiety, over sensitivity, attention and focus issues, mental acuity, memory and many other symptoms can occur. You can see there is some significant overlap with some of these symptoms with the behavioral symptoms that occur with ASD.
If you can identify and remove any potential immunological issues with children with ASD, it possible to effect them in many ways.
Remove a possible antibody trigger affecting folic acid delivery to the brain, improving folate levels and supporting neuronal development
Remove a possible allergenic food causing other physical symptoms in the child (digestive, immune system, energy, etc.)
Remove a possible adrenal system draining process, affecting their energy, anxiety, focus and concentration and sleep.
Autism Spectrum Disorders and Vaccinations
This is far too broad reaching and complex topic to discuss in this article at length. There are a few key points that correlate with the immune aspect to this article that should be brought forth however.
There has been debate for years as to the possible cause / effect relationship between childhood vaccinations and autism and learning disorders. The complementary medicine world has been trying to prove the link and have been unable to to date. The conventional medical world has been trying to disprove the link and they haven't been successful either. Anecdotal evidence has shown some correlation but long term studies haven't supported this idea. If we examine the idea of molecular mimicry (discussed in the Food Allergy article) and how it relates to vaccines, it can provide some answers to this age old debate.
The same part of the immune system that reacts to a vaccination (B cell, T cell, Antibody system) is the EXACT same system that reacts to a food for a delayed onset food allergy. When you get a vaccination, the immune system recognizes it as being foreign, and produces antibodies to the vaccine, designed to travel through the body and look for anything that looks like the vaccine to attack. The exact same thing can happen when an allergic food gets in your system.
When you get a vaccination, you are being given a "dead" viral protein (unable to reproduce). Your immune system will produce millions of antibodies to this vaccine and the antibodies will float around your system for weeks to months looking for anything that looks like the vaccine to attack. The important thing to note here is that the viral vaccine is unable reproduce, so eventually the antibodies to this vaccine will naturally decline and disappear if the vaccine is not repeated. When you eat a food you're allergic to, the antibodies will be produced to the food each time you eat the food.
It's possible (and in my opinion likely...) that antibodies to vaccines can bind to and block the same folate transport receptors that the dairy (casein) antibodies did in the research study outlined above. The difference here is that the antibody "block" against these receptors will only last as long as the antibodies last in the system. Once the vaccine antibodies dissipate, the block on these receptors goes away, and normal transport could resume. The "autistic" response in this case might be very transient or short lived This could explain why the long term studies on vaccinations and ASD don't show significant correlation. Shorter term studies have shown transient ASD like responses to vaccines, but once the child goes a period of time without the vaccinations, the symptoms commonly diminish.
Now consider a dietary trigger for the folate receptor auto-antibody. Every time the child eats the trigger food, they are producing an extended auto-antibody response. If this child eats this food regularly, the antibody levels would never diminish and the folate receptor block could continue long term, leading to more pronounced and possibly more permanent neurodevelopmental issues.
To summarize a treatment approach based on this article.
Identify any potential immunological "triggers" for possible auto-antibodies and remove them (dietary, environmental, etc.)
Provide neurological supportive supplementation based on the patients symptoms.
Identify and correct other biochemical hormonal imbalances associated with the immunological dysfunction (adrenal, pituitary, etc.)