Autoimmunity

Autoimmunity is a condition where a person’s immune system is unable to differentiate “self” from “nonself” components. In such cases, the immune system develops “self reactive” antibodies and/or cells that lead an attack against the body’s own tissues as if they were foreign invaders. Autoimmunity is well defined in diseases such as rheumatoid arthritis and systemic lupus. However, autoimmune reactions to brain tissues also may be involved in a subset of autism cases. The presence of antibodies to brain tissues is abnormal and can be detrimental to CNS development and function. Several studies have demonstrated the presence of autoantibodies specific to various CNS tissues in subjects with autism and animal models, including myelin basic protein, neuronal and glial filament proteins, and several other unidentified brain antigens. These studies show that autoimmune activity can be associated with autism in some (but not all) cases.

It is difficult to determine whether these autoantibodies contribute to the development of the disorder or if they are a consequence of the disease. Gastrointestinal Immunity Gastrointestinal (GI) symptoms, including abdominal pain, bloating, diarrhea and constipation have been reported in a subset of subjects with ASD. Those with GI symptoms have been found to have inflammatory cytokine profiles in mucosal immune cells and peripheral blood compared to controls. The exact relationship between GI symptoms and ASD is unclear. The GI tract is the site of extensive and specific immune activity, and it has been proposed that immune-mediated GI pathology may lead to systemic immune activation and inflammation in the brain. However, there is yet to be concrete data to support this claim.

Conclusion

There appears to be a strong correlation between immune dysfunction and autism, though the extent to which aberrant immune activity is involved in the pathogenesis of autism is unknown. ASD must be recognized as a spectrum of diseases, each of which may have a distinct cause and disease process. Future research should focus on finding biological markers for ASD and its variations. This breakthrough would open the door for early testing and intervention during the first few years of life, a time that is critical for brain and neural development.

Paula Goines, B.S., Paul Ashwood, Ph.D., and Judy Van de Water, Ph.D., are affiliated with the University of California at Davis.

Van de Water is an associate professor in the department of internal medicine.

Ashwood is an assistant professor in the department of medical microbiology and immunology.

Goines is a graduate of the University of California, Davis, and is a Ph.D. student in the immunology graduate group. All three also are affiliated with the UC Davis MIND Institute.