Link Between Autism and Immune System

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The immune system and autism.

Is there a connection? Scientists have found an association of several molecules in serum and cerebral spinal fluid with autism that are associated with immune-related signaling pathways.

Why is cerebrospinal fluid important? Well, cerebrospinal fluid is a liquid found in the brain and the spine, which is the central nervous system. The central nervous system controls so many functions in our bodies – like muscle movement, thinking, planning, and very importantly, sensory receiving and perceiving.

This is the first study to analyze cerebrospinal fluid and serum concentrations of a large set of potential biomarkers in the cohort of twins. It is very exciting!

Biomarkers

Currently, there are no robust biomarkers available for detecting autism. I have several videos on how do you make an autism diagnosis? If you’re interested, here are the links.

Biomarkers are important as they provide a measurable and objective way to diagnose and characterize diseases and disorders. It would be great if autism had one or more biomarkers. Previous studies of peripheral biomarkers have revolved around altered metabolism and gut permeability as well as inflammation.

The Study

This is a twin study and this study is from the Roots of Autism and ADHD Twin Study in Sweden, and it aims to identify biomarkers for autism from the serum of 127 participants as well as cerebrospinal fluid from 86 participants. Cerebrospinal fluid is not necessarily the easiest to get. You have to do a lumbar puncture that’s obviously a lot more complicated than a blood test.

By studying a cohort of twins, this research is exploring the shared factors between twins, including genetics and shared environment. With autism, there’s this really dynamic interplay between genetics and environment, and this study is trying to tease out which can be contributed to which. In total, 203 proteins were examined using commercially available immunoassay panels. The protein studied covered a wide range of biological processes, including inflammatory response, immune response, cellular metabolic processes, and cell-cell signaling. You can see the proteins explored in this study are wide-ranging. They cast a large net.

Results

Here are the results. In individuals: After preliminary analysis, 6 cerebrospinal fluid and 23 serum proteins were identified that could be related to the severity of autistic behavior. There’s a particular protein called the CSTB, and that protein was identified with the highest autism trait correlation.

Here are the results for the twins. There was no correlation for cerebral spinal fluid. Correlation found in serum predominantly for B cell-activating factor. It’s called a BAFF. There was no significant correlation between cerebrospinal fluid and serum proteins.

Let’s get a little more granular into the results for the BAFF serum.

BAFF serum protein plays an important role in immune function also known as tumor necrosis factor. In general, high levels of BAFF indicate systemic auto-immune disorders so it’s interesting that this is a protein that came out as important. There are some papers out there that link autism to more of an auto-immune disorder so this is very interesting research. Per the study, BAFF was the only biomarker that survived the twin pair analysis, and BAFF is interconnected on the interaction map and has a variety of functions including immunity and neuro-development.

Let’s talk a little bit about the results for the CSTB protein. So CSTB protein from the blood serum it plays an integral role in brain physiology. So BAFF was more general. It was very interconnected. The CSTB has a very integral role in brain physiology. CSTB protein in the serum had the strongest association with autistic traits and autism. You might be wondering what does CSTB do specifically and it protects against leakage of proteases from lysosomes. However, CSTB protein is located far out on the interaction map of genes being indicative of its very specific function and lack of coregulation with other molecules. So BAFF was very general kind of involved in a little bit of everything and CSTB is much more specific and involved in brain physiology.

Conclusion

Conclusions from the paper:

“To conclude, we report an association of Several molecules in serum and cerebral spinal fluid with autistic traits and autism with significant enrichment in immune-related signaling pathways.”

Immune function is important in your child with autism and many times the immune system is overwhelmed in children with autism.

We’re starting to understand a little bit more as more and more of these research articles come out and a special thank you to Esha. Esha is a nutrition intern that’s been working with me for this past semester. She’s from Cornell University. She’s an absolute pleasure to work with and extremely brilliant.

Also, here are some references:

Journal of Neurochemistry. 2021;158:798-806

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