By Paula Goines, B.S., Paul Ashwood, Ph.D., and Judy Van de Water, Ph.D

The exact cause of autism spectrum disorders (ASD) is not well understood. ASD is likely to involve a combination of genetic, immunological and environmental factors, and may encompass several diseases with distinct origins. Currently there are no biological markers for ASD, and diagnosis is based solely on behavioral criteria.

A recent, dramatic rise in the incidence of ASD has sparked an intense effort toward a greater understanding of the disease. Several studies have linked immune system abnormalities to autism.

Aberrant immune activity during critical periods in development potentially could enhance neurological disorders. The following is a brief summary of the current research correlating ASD and immune dysfunction.

Cytokines

Cytokines are proteins made by immune cells that regulate the nature, intensity and length of an immune response. Additionally, cytokines are important in the development and health of the central nervous system (CNS). Thus, abnormal cytokine production during critical windows of brain development could have long-term effects on the health of the nervous system.

Increased levels of proinflammatory cytokines such as TNF-alpha, and decreased levels of anti-inflammatory cytokines such as IL-10 have been observed in children with ASD. Imbalanced levels of these cytokines can augment inflammation and cause excess damage to tissues.

Cytokines secreted by T cells can be categorized into two major subsets termed TH1 (associated with a cell response and inflammation) and TH2 (associated with allergies and asthma). One study found elevated proportions of TH2-producing lymphocytes in subjects with ASD when compared with controls.

However, another study demonstrated a TH1-skewed cytokine profile. A third study found increased levels of both TH1 and TH2 cytokines without a compensatory increase of the regulatory cytokine IL-10 in a small group of ASD children. These contrasting findings may represent different categories of ASD, a theory that may be explored by taking behavioral characteristics into account.

The CNS contains different cell types that have a role both in brain function and the CNS immune response. A study in 2005 of brains from people with ASD showed inflammation characterized by activation of these specialized brain cells. Additionally, altered cytokine patterns were observed in the brains and cerebrospinal fluid of subjects with autism compared to controls. Abnormal immune responses in these brain cells in people with ASD may influence neural function and development, and could indicate an attempt by the activated cells to repair CNS damage.