Lower risk of autism associated with average levels of immune markers measured at birth

Reviewed by Emily Henderson, B.Sc.November 10, 2020

The causes of autism spectrum disorder (ASD), including genetic and environmental factors, are not fully understood. Many studies have already shown that severe maternal infection during pregnancy is associated with an increased risk to offspring in both humans and animals. New research, however, shows that lower risk of ASD is associated with mean levels of an immune marker measured at birth, while too much or not enough was linked to increased risk.

The report of researchers from the Karolinska Institute in Sweden appears in Biological psychiatry, published by Elsevier. The study is based on the idea that the developing brain may be particularly vulnerable to immune signaling disorders and exposure to inflammation.

We studied a set of molecules called acute phase proteins that are part of the innate immune system, which is our first line of defense against infection and always monitors the body for signs of invasion. These molecules circulate in our bloodstream all the time, but they can rapidly increase after exposure to infection.

Renee Gardner, Ph.D., lead author

The researchers examined the proteins from birth blood samples from nearly 1,000 children with ASD and over 1,000 healthy controls from the Stockholm Youth Cohort, a Swedish health registry. Babies born with high levels of a classic marker of inflammation, called C-reactive protein (CRP), were at higher risk for ASD.

The thinking based on previous studies was simply that too much inflammation hurts the developing brain. Surprisingly, however, the lowest risk was associated with mid-range CRP levels. “This means that too much inflammation may actually be bad for the developing brain, but it could also be too little, explained Dr. Gardner.

“Among infants whose mothers were hospitalized for an infection during pregnancy, those who were able to produce a little more of these acute-phase proteins tended to have a lower risk of autism. Hence. it seems that a greater ability to respond to the surrounding environment could translate into a lower risk of autism, “he added.

In a second part of the study, the researchers compared the levels of immune proteins at birth between infants with ASD and their siblings without ASD. The unaffected siblings had higher levels of immune markers than those with ASD. “This is interesting because siblings share about half of their DNA and environment within the womb and during the first few days of life they are likely similar between siblings,” said Dr. Gardner.

Another interesting finding concerns the risk of ASD represented by maternal anemia or iron deficiency. Among children whose mothers were anemic, those with the highest levels of ferritin, an iron-binding protein in the blood, an indicator of iron levels, were protected from autism. This finding suggests the importance of iron status for the developing brain and may explain the anemia-related risk of neurodevelopmental disorders.

“The association between immune system activation markers at birth and the resulting risk of autism could be important,” he said. Biological psychiatry publisher John Krystal, MD. “We have looked for avenues for the prevention of ASD, such as mechanisms that might be targeted by drugs before symptoms appear. However, we need to be cautious because we don’t yet know if immune activation is a contributor or a marker of risk. for autism. “