heterogeneous neurodevelopment

“Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental conditions presenting in early childhood with a prevalence ranging from 0.7% to 2.64%. Social interaction and communication skills are impaired and children often present with unusual repetitive behavior. The condition persists for life with major implications for the individual, the family and the entire health care system. While the etiology of ASD remains unknown, various clues suggest a possible association with altered immune responses. Inflammation in the brain and Central Nervous System (CNS) has been reported by several groups with notable microglia activation and increased cytokine production in postmortem brain specimens of young and old individuals with ASD.

Moreover, several laboratories have isolated distinctive brain and CNS reactive antibodies from individuals with ASD. Large population based epidemiological studies have established a correlation between ASD and a family history of autoimmune diseases, associations with MHC complex haplotypes, and abnormal levels of various inflammatory cytokines and immunological markers in the blood.

In addition, there is evidence that antibodies that are only present in some mothers of children with ASD bind to fetal brain proteins and may be a marker or risk factor for ASD. Studies involving the injection of these ASD specific maternal serum antibodies into pregnant mice during gestation, or gestational exposure of Rhesus monkeys to IgG subclass of these antibodies, have consistently elicited behavioral changes in offspring that have relevance to ASD. We will summarize the various types of studies associating ASD with the immune system, critically evaluate the quality of these studies, and attempt to integrate them in a way that clarifies the areas of immune and autoimmune phenomena in ASD research that will be important indicators for future research.”

Immunological Evidence

“In conclusion, various types of immunological evidence (brain antibodies, serum cytokines, family history, and immunogenetics) point to a relationship between ASD and the immune system. Since some of these studies lack robust controls and many focus on only one type of immunological evidence in isolation, our international group suggests that future research focus on intensifying studies analyzing immunological aspects of ASD with proper controls in a more integrative fashion.

One question for further research involves the precise characterization of the nature of the relationship between ASD and the immune system. None of these studies sufficiently explain whether the immune system underlies the pathology of ASD in a causative way, whether immune interferences create vulnerability to other pathogens responsible for ASD, or whether a third, yet unknown factor is responsible for both the pathology of ASD and for the aberrant immune response in ASD. Further research should consider the potential relevance of assessing the autoimmune aspects associated with ASD according to systematic guidelines for autoimmune diseases described by Shoenfeld et al. and Rose and Bona.”

Publication: Journal of Autoimmunity, 2013

Authors: Benjamin Gesundheit, Joshua P. Rosenzweig, David Naor, Bernard Lerer, et al.

This article presented questions which researchers are still trying to better answer. Click Here to see our additional publications in this series to follow where our current research is heading.