The human leukocyte antigen (HLA) genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects. 1. Autism Leo Kanner first described autism in 1943 [1] after finding 11 children with common symptoms of obsessiveness, stereotypy, and echolalia at Johns Hopkins University. Autism remained an esoteric disorder for several decades until physicians and parents connected these symptoms with an increasing number of patients. It is important to note that the diagnostic criteria have been modified over the years to include a broader category of symptoms, thus increasing the number of children diagnosed with the disorder, now referred to as Autism Spectrum Disorder (ASD) [2]. Currently, the Centers for Disease Control and Prevention (CDC) states that the incidence of ASD is 1 out of 110 children in the United States [3]. The severity of ASD varies greatly with the most severe forms, much like Kanner autism, displaying language regression, seizures, and lower IQ. Altevogt et al. [4] have suggested that autism, or more properly ASD, is not a single disorder, but a collection of similar disorders each with different characteristics and perhaps etiologies. Even after several decades of research, there is much debate around the world on the etiology of ASD. It is clear that ASD results from abnormal brain development in either the prenatal period or infancy stage of life. Exposure to mercury, maternal viral infections, autoimmune disorders, and the inheritance of certain gene combinations have been implicated in the etiology. Unfortunately, none of these areas have given clear answers as to the etiology. Fortunately, psychologists have made significant strides in treating
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