children with regressive autism (23 out of 25 patients) compared to normal controls and patients with cerebral palsy. Epithelial IgG and complement C1q deposition was also seen in 23 out of 25 children with autism, and not seen in the other groups. It was suggested that this autoimmune enteropathy may lead to altered cognitive functioning through failure to detoxify neuroactive substances originating from the gut. In other studies, ileal lymphoid hyperplasia and lymphocytic colitis, with striking infiltration of CD8 and T cells, have been reported in children with regressive autism (Wakefield et al., 1998, 2000). It should be pointed out that these GI studies have all been in children with regressive autism, which is an uncommon38 subtype of autism. It is thus difficult to know how these findings apply to the majority of people with autism. More importantly, it is not clear whether the autism is the cause or the consequence of the GI abnormalities.
Although a number of studies have suggested immune dysregulation in autism, there is as yet no evidence that these findings are directly related to the pathogenesis of autism. Unlike what is known about neuroimmunological disorders that affect the brain, such as multiple sclerosis and acute disseminated encephalomyelitis, there is no evidence of immune activation or an inflammatory process within the autistic brain. Neuropathological studies of autism have revealed no evidence of cerebral inflammatory lesions or microglial activation, which is a common feature in immune-mediated encephalitis (Bauman and Kemper, 1997). However, there are very few autopsy studies of brains from people with autism and this has not been fully investigated. Analysis of CSF from young children with autism, including screening for sensitive inflammatory markers such as quinolinic acid and neopterin, has also found no evidence of inflammation (Comi et al., 1999). The sample size in these studies is small, however.
As mentioned, autoantibodies to cerebral antigens, including MBP, have been found at higher titers in children with autism compared to controls. It is important to note, however, that these studies all evaluated serum and not CSF or brain tissue. Furthermore, it should be realized that not all autoantibodies are pathogenic—indeed, they are found in healthy individuals with no evidence of autoimmune disease. Some of the factors that determine the pathogenicity of a particular autoantibody include its affinity or avidity of binding to the autoantigen, its access to the autoantigen, and its ability to fix, complement, and facilitate cell-mediated death. With respect to the pathogenicity of serum anti-MBP antibodies in people with autism, no signs of demyelination have been found either on MRI or neuroanatomically in children with autism (Rumsey and Ernst, 2000). It is thus debatable how relevant serum anti-MBP antibodies may be to the pathogenesis of autism. It is not clear whether the dysregulation precedes the autism or is part of the syndrome.
Some investigators have tried immunotherapies, such as corticosteroids and intravenous immunoglobulin, in people with autism on the assumption that immune