Autism is an enigmatic childhood disorder of unknown origin. It is characterized by developmental, language, and social deficits, ranging in severity from patients with profound deficits to individuals that are high functioning. Although the underlying etiological basis of autism has eluded researchers, the genetic heritability of autism is quite strong 1
. Specifically what genes are involved and how they contribute to the disease phenotype is unclear.
Many theories regarding the biological basis of autism have been suggested, including neurodevelopmental, exposure to environmental toxins, particularly to mercury 2
, and immune 3
hypotheses. More recently, theories of hyper-systemizing and assortative mating 4,5
and hyper-dopamine 6
have been proposed. At this time there is little definitive evidence to support any single theory of the fundamental biological nature of autism.
Numerous reports have described imbalances in immune and inflammatory processes in autistic patients, including aberrations in antibody levels, cytokines, and cellular subsets 7,8,9,10,11,12
. Additionally, recent reports have described an increased frequency of HLA-A2 13
and HLA-DR4 14
antigens in autism. Interestingly, epidemiological studies have provided evidence for the association of asthma and allergies 15
or autoimmune disorders in families with autistic children 16,17,18,19
. The exact significance of immune abnormalities and the relationship of infections, immunizations, allergies, inflammation, or other aspects of immune response to disease etiology are unclear and controversial. Alterations of immune and inflammatory processes in autism have recently been reviewed 3,20,21,22-24
One of the challenges in the early study of the molecular basis of classical autoimmune disorders was the attempt to establish the relevance of highly variable and fluctuating immune serum proteins and cell populations to disease etiology. That is, are fluctuations in any set of cytokines, immune mediators, or T cell populations, causative or are they epiphenomena due to peripheral effects of target tissue destruction, transient common infections, or more importantly, are they echoes of long ago infections. There is an ever present “which came first, the chicken or the egg” nature in the study of highly variable immune mediators. Are oligoclonal antibody bands found in the CSF of multiple sclerosis patients 25
related to the etiology of the disease or are they end stage phenomena? Do alterations in cytokines from a patient with systemic lupus erythematosus have a role in disease etiology or are they late stage responses to tissue destruction brought on by other mechanisms? Similarly, are immune aberrations in autism disease causing or are they epiphenomena?