Review: Immune Dysfunction in Autism Spectrum Disorder, Part 1

I don’t frequently see abstracts that I feel strongly enough about to spend the money to purchase the full text article. However, the paper by Estes and McAllister that appeared in Nature Reviews Neuroscience (16:469-486, 2015) is exceptional. It is well written, packed with references to original research, and understandable to non-immunologists. However, I am going to summarize the key points in my blog for those of you with limited time or lack of access to the article. There is so much to say that it is too long for a typical blog post, so I will break it into parts.

As I have posted numerous times on my website and social media pages, it is becoming increasingly clear that genetics, environmental factors, and timing of insults early in development contribute to immune system dysfunction and behaviors diagnosed as “autism”. Most of our evidence comes from recovered children who have had their autism symptoms addressed medically, have gradually lost all of the behaviors associated with autism through intensive rehabilitation and have gone on to lead normal, productive lives (1, 2). In the last few years, animal models have also been used to demonstrate the impact of maternal immune activation, using viral mimics during pregnancy, as one of the environmental risk factors.

Literature review
Literature review

The first key point is that immune dysregulation has a central role in autism spectrum disorder (ASD). It is estimated that there is up to a 50% increase in the odds of an ASD diagnosis among children with a parent with an autoimmune disorder. Although paternal and maternal autoimmunity (or a general family history of autoimmune disorders) contribute to the risk of ASD, it is mainly maternal immune disorders that account for most of the risk. This is not ‘the same old’ “blame the mother”, “refrigerator” argument formerly used to explain ASD. Remember that a pregnancy is somewhat like a graft or a transplant situation. The fetus has paternal gene products that are foreign to the mother, and pregnancy is a time when the immune system is down-regulated, or quieted, so that the mother’s body does not “reject” the child. Gestational diabetes and increased maternal age both increase or change inflammatory pathways, resulting in altered development of the baby’s immune system. Autoimmunity, including MS, rheumatoid arthritis, type 1 diabetes, and lupus alter the cytokine environment by preventing IL-10 production. It is the cytokine responsible for giving the child protection from immune attack by suppressing the mother’s immune system, making it tolerant to the developing fetus.

There are also variants of several genes related to the immune system, including the major histocompatibility antigens (human HLA types), complement genes, and cytokine receptors that are associated with ASD. You are not in control of genetics, so the pieces in your control are optimizing your own health, your child's health and overall environment.

You will probably not be told any of this when you are pregnant, though! So, I will gently suggest, based on this research, it would be wise to take extra precautions with a baby who is already at risk if you have autoimmunity. When your baby is born, you are in full control of environment and what products going into, on, or around your child. If it means saying "no" to a visitor who is ill, or not taking your child to a crowded gathering/public space during flu season, use common sense, especially if you are not breastfeeding.

Taken together, scientific data continue to accumulate that demonstrate that the immune system is a critical point of convergence of genetic vulnerability and environmental insults, particularly infectious organisms or anything that weakens, or challenges the immune system.

  1. Hinds, Marcia, with Ryan Hinds. "I Know You’re In There: Winning Our War With Autism". 2014. Hindsight Press, Los Angeles, CA.
  2. Goldberg, Michael J, with Elyse Goldberg. "The Myth of Autism: How a Misunderstood Epidemic is Destroying Our Children". 2011. Skyhorse Publishing, New York, NY.