New Study Points to an Association, Although More Research Needed
An ideal immune system recognizes foreign organisms (bacteria, viruses, parasites, and fungi) while efficiently and rapidly destroying these invaders. A second infection from the same foreign organism is prevented by a well-functioning immune system as it recalls the method to destroy the invader another time.
One of the immune system’s most critical functions is to distinguish between organisms that are self and non-self. If that determination process malfunctions, the body may form proteins called autoantibodies. In simple terms, autoantibodies are antibodies that attack the body’s own tissues, cells or cell components leading to a state called autoimmunity. Autoantibodies can cause many types of autoimmune disease.
Although there are still no definitive answers for what causes autism spectrum disorder (ASD), there is a good deal of research that points to an interaction between genetics and environmental factors as a possible mechanism for causation. Over the past two decades, associations between immune system abnormalities and autism have been linked. A new systematic review from Harvard Medical School, among other institutions, examines this intricate relationship.
At the beginning of this innovative meta-analysis, the research team maintains that autoimmune disorders including Type 1 diabetes and inflammatory bowel disease have been diagnosed in individuals with autism as well as their family members. Likewise, they report that mothers with other autoimmune diseases such as rheumatoid arthritis and systemic lupus were more likely to have children with ASD. Additionally, the researchers stated that autoantibodies had been detected in patients with autism and other behavioral disorders, including Tourette’s syndrome, attention deficit hyperactivity disorder, and obsessive-compulsive disorder. Due to these observations, the team came up with three questions they hoped to answer through their analysis. First, could the presence of autoantibodies become an autism diagnostic tool? Second, are autoantibodies responsible for the development of autism? Finally, would treating these autoantibodies lead to new treatments for autism?
To find the answers to these questions, the researchers started with a cohort of 420 studies to analyze. Only 19 out of the 420 studies qualified for their review, after their inclusion criteria were applied. Ultimately, these 19 studies included 1,610 ASD patients and 1,299 healthy controls. The team identified six different autoantibodies which were the focus of at least two studies: folate receptor a autoantibody (FRAA), anti-MAG and anti-MBP antibodies, anti-ribosomal P protein antibody, anti-endothelial cell antibody, and antinuclear antibody (ANA).
The aim of their investigation was simple. The research team wanted to find out if there are abnormalities in the identified autoantibody(ies) from serum or cerebrospinal fluid of individuals with ASD compared to neurotypical controls. The answer was clear-cut. Children with autism do have higher levels of antibodies reactive to FRAA, anti-MAG and anti-MBP, anti-endothelial cell antibodies, anti-nuclear antibodies, and ANA compared to neurotypical controls. Also observed in some children with ASD were hypersensitivities to gluten and viral vaccines such as MMR.
Part of the study’s conclusion states, “Given the significant between-study heterogeneity, small sample sizes in individuals included studies, and lack of relevant information, the quality and level of our overall evidence is limited and future large scale and well-designed studies are warranted to either confirm or refute the findings in precious studies.”
Sadly, the authors concluded that there was not enough high-quality evidence to develop guidelines for routine autoantibody testing and screening. Therefore, they were unable to achieve their original three goals of identifying a diagnostic or screening tool or discovering treatments for autism through this research.
The researchers remain hopeful. They finish the study by declaring, “With increasing basic and clinical research in this field and better understanding of genetic, epigenetic and protein-level mechanisms of molecular mimicry, it is possible that in the near future, we can develop specific diagnostic panels for autoimmune encephalitis associated with ASD, identify immunomodulatory targeted therapies and establish management guidelines for auto-immune-mediated subtypes, in order to optimally modify or reverse the core symptoms of the ASD patients.”
References
Keith Elkon, Paolo Casali. Nature and Functions of Autoantibodies. Nature Clinical Practice Rheumatology. September 2008.
Ana Lleo, Pietro Invernizzi, Bin Gao, Maura Podda, M. Eric Gershwin. Definition of Human Autoimmunity—Autoantibodies Versus Autoimmune Disease. Autoimmunity Reviews. December 2009.
Tianle Zou, Jun Liu, Xueying Zhang, Huilin Tang, Yiqing Song, Xuejun Kong. Autoantibody and Autism Spectrum Disorder: A Systematic Review. Research in Autism Spectrum Disorders. Volume 75. July 2020.
