Autism and the Immune System

Autism is a Complex-System Disorder

The development of autism has long been recognized as having a complex interplay between genes and environment. Many theories with compelling evidence have been put forth regarding the biological basis of autism, including: environmental toxicity; gut dysbiosis; cell danger response; hyper-dopamine; assortative mating, and more. However, no single theory carries definitive evidence as being the sole biological basis of autism.

Personally, I don’t feel that we will ever arrive at a single cause of autism. I believe it is a complex-system disorder that can be provoked by a number of triggers, and thus treatment will require an individualized comprehensive approach. In this article, we will cover the research that proposes an immune-based connection. While this may not be the biological basis of all cases of autism, it has profound implications for many!


I believe Autism is a complex-system disorder that can be provoked by a number of triggers, and treatment will require an individualized comprehensive approach. Click To Tweet


General Immune System

A great number of articles describe immune and inflammatory imbalances in autistic children, including alterations in antibody levels and high levels of inflammatory cytokines. Perinatal and early childhood infections, vaccinations, and allergies have all been implicated as potential triggers in the development of autism, but these factors are still very controversial at this point.



Numerous reports have shown an increased association between atopic conditions (allergies, eczema, or asthma) early in life and the development of autism and ADHD. In one study, allergy symptoms were found to be 5 times higher in children with autism than neurotypical children. In another study, eczema and asthma were found to be much more prevalent in children with Aspergers compared to age matched controls (87% vs 7%).

Additionally, a cohort study shows that children with autism whose mother had asthma or allergies during pregnancy had more severe social impairment. Parents of children with autism more commonly report food allergies and sensitivities in their child. Furthermore, both atopic conditions and autism have shown a significant increase in prevalence at similar rates over the last 30 years. With this evidence and much more, it has been suggested that autism may be mediated by factors associated with atopic conditions, specifically mast cell activation.

Mast Cells Activation and Autism

Mast cells are immune cells that are best known for their role in allergies. When mast cells are activated by an external stimuli, such as an allergen, infection, or insect bite, they release various inflammatory mediators and peptides that cause the classic allergic symptoms. These symptoms can range from hives, itching, difficulty breathing, rapid pulse, diarrhea, nausea, and more.

When mast cells are activated, in the case of allergies or eczema, these inflammatory cytokines can also have other undesirable effects, such as disrupting the blood brain barrier. One cytokine that is released from mast cells and found in high concentrations in the brain of children with autism is IL-6. Studies with mice also show that high levels of serum IL-6 is associated with autistic behavior. For this reason, mast cells have been implicated as the “immune-gate to the brain” and an important factor contributing to the neuroinflammation found in autism.

Post-mortem studies have found that the brains of children with autism show altered blood-brain barriers, high levels of inflammatory cytokines, immune activation, and evidence of chronic inflammation. Put simply, it is believed that systemic immune activation from allergies, eczema, and asthma can trigger inflammation within the brain through various inflammatory mediators that are released from mast cells. While allergens are well-known mast cell activators, other environmental exposures and infectious agents can also trigger mast cell activation, including: pesticides, heavy metals, bacteria, mold, viruses, and even stress.

Autoimmune Disease

Family history and personal history of autoimmunity has been found to be more common in children with autism. One study found that 46% of children with autism had 2 or more family members with autoimmune disease. Another study found that there is a 50% higher odds of being diagnosed with autism by age 10 among children whose parents had any autoimmune disease. Maternal autoimmunity during pregnancy is a recognized risk factor for the development of autism. Although the exact mechanism is not certain, it is believed that maternal autoimmunity may influence brain development by flooding the fetus with inflammatory cytokines in utero or by altering the child’s own immune response in early development.

Additionally, recent reports show an increased frequency of HLA-A2 and HLA-DR4 antigens in autism, both of which are also associated with an increased risk for various autoimmune disorders. Taken together, we now understand the immune system is an important influence in healthy neurodevelopment, and immune dysregulation, especially during critical windows of development can have long lasting impact on neurodevelopmental outcomes.

The Hygiene Hypothesis

With a drastic rise in autoimmune disease, atopic conditions, and autism, we must begin to ask WHY? While I personally believe environmental toxicity may account for a great deal of this rise, the “Hygiene Hypothesis” also presents compelling evidence. According to the Hygiene Hypothesis, a decreased incidence of infection and exposure to potential pathogens early in life contributes to an immature or dysregulated immune response, leading to more maladaptive immune responses, such as that seen in conditions such as autoimmunity and allergies.

This would explain why there is virtually no presence of allergies, autoimmunity or autism in developing countries, whereas these conditions are quite prevalent in industrialized western societies. Supporting research shows an increase in atopic skin disorders after antiparasitic treatment, and successful treatment of autoimmune conditions has been found with the use of parasites. The Hygiene Hypothesis proposes that early childhood exposure to microorganisms within our environment is crucial to the development of a tolerant immune system, and being hyper-vigilant about cleanliness could increase our child’s risk of developing an immune disorder.

Closing Remarks

There is strong evidence of Immune dysregulation as a driving force in the development of autism, and catching it early on is key! A few parting thoughts include:

  • If you have a personal history of autoimmune disease or atopy, it is important to do as much as possible before conception to stabilize your immune system!
  • A comprehensive autism intake should include questions regarding your family history of autoimmune disorders, atopic conditions, and autism.
  • A comprehensive laboratory workup for autism, should include assessment of the immune system.
  • Mast cell stabilization and immunomodulation is a key aspect of treatment in many cases of autism.

Written by Dr. Ari Calhoun

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