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February 22nd, 2021 

The newsletter metrics say that roughly 10% of the readers only tune in to the COVID newsletters whereas 90% read every week. Therefore, I replayed this article from last week based on its critical importance for all to bear witness to.

Autoimmune based Autism Spectrum Disorder or ASD - Maternal autoantibody induced autism accounts for roughly 18% of all autism cases to date. The study in Molecular Psychiatry from January 2021 found that through machine learning they could identify autoantibody biomarkers that were 100% associated with autism when found in a specific pattern. In other words, the mothers of autistic children with autoimmune antibodies targeted against certain proteins in the infant's developing brain in utero were noted in 100%

of cases. This is a subset of autistic spectrum disorders only, however, this may actually be the front end of the wave that shows that all ASD may be autoimmune in a maternal to neonate transmission pattern.

The authors state, "This is the first report that uses machine learning subgroup discovery to identify with 100% accuracy MAR ASD-specific patterns as potential biomarkers of risk for a subset of up to 18% of ASD cases in this study population." (Ramirez-Celis 2021)

The mechanism seems to be autoimmune destruction of critical proteins in the developing mind of a baby. The proteins are collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2), guanine deaminase (GDA), lactate dehydrogenase A and B (LDHA, LDHB), stress-induced phosphoprotein-1 (STIP1), neuron-specific enolase (NSE)and Y-box binding protein 1 (YBOX).

Each one of these proteins has the following functions: For example, CRMP is involved in neuronal network formations. Antibodies against CRMP can alter neuronal formation and networking leading to dysfunctional brain activity. (Ohtani et. al. 2019)(Schmidt et. al. 2007) GDA is an enzyme involved in neuronal microtubule assembly. LDH A/B are involved in energy glycolysis pathways all over the body. Dysfunction in the neuron can affect neuronal growth and development. Every antibody that is found will likely be attacking a neuronal activity or a metabolic pathway that leads to the phenotype of the disease that we call autism spectrum disorder.

The animal models of passive antibody transfer during pregnancy are a proof of mechanism for antibody induced disease and not merely a biomarker.

This data has profound implications for predicting future autism risk in a pre-pregnancy state. If we knew that a mother had these specific biomarkers in her blood stream, then her child would be orders of magnitude higher risk for developing autism spectrum disorders. There may be a future for pharmaceutical biological antibodies to bind and neutralize these antibodies to prevent autism. This is the first set of hopeful evidence in the prevention category.

For me, this data adds to the bigger and more obvious answer. As a society, we need to grapple with the reality that our collective lifestyle choices put us at risk for autoimmune antibody development via excessive and chronic inflammation and then downstream risk.

 Dr. M

Read these three newsletters from 2018 and associated articles to better understand autoimmunity and how to prevent it.

Newsletter 1
Newsletter 2
Newsletter 3
Proal Current Opinions in Rheumatology
Colpitts J of Immunology