Autism may involve an autoimmune pathogenesis in a subgroup of patients. The frequency of anti-nuclear antibodies in 80 autistic children and their relationship to a family history of autoimmunity were studied, compared with 80 healthy, matched children. Children with autism had a significantly higher percent seropositivity of anti-nuclear antibodies (20%) than healthy children (2.5%; P < 0.01). Fifty percent of anti-nuclear antibody-seropositive autistic children had an anti-nuclear antibody titer of >/=1:640 (very high positive); 25%, >/=1:160 (high positive); and the remaining 25%, 1:80. All anti-nuclear antibody-seropositive healthy children had anti-nuclear antibody titers of 1:80. A family history of autoimmunity was significantly higher in autistic children (47.5%) than healthy controls (8.8%; P < 0.001). Anti-nuclear antibody seropositivity was significantly higher in autistic children with a family history of autoimmunity than those without such history (36.8% and 5%, respectively; P < 0.001). Anti-nuclear antibody seropositivity had significant positive associations with disease severity, mental retardation and electroencephalogram abnormalities. Autoimmunity may play a role in a subgroup of children with autism. Further studies are warranted to assess anti-nuclear antibody seropositivity, other markers of autoimmunity (e.g., brain-specific autoantibodies), and the role of immunotherapy in children with autism.
There is increasing evidence of immune involvement in both schizophrenia and autism. Of particular interest are striking abnormalities in the expression of immune-related molecules such as cytokines in the brain and cerebral spinal fluid (CSF). It is proposed that this represents a permanent state of brain immune dysregulation, which begins during early development. One possibility is that maternal infection, a known risk factor for schizophrenia and autism, sets this immune activation in motion. Several animal models are being used to investigate this hypothesis. There is also recent evidence that, among schizophrenic subjects, those associated with maternal infection display a distinctive pathology, which suggests that diverse causes for this disorder may explain some of its heterogeneity. The human and animal results related to immune involvement suggest novel therapeutic avenues based on immune interventions.
Accumulating evidence indicates that immune dysfunction is associated with autism disorders in a significant subset of children. Previous reports have shown abnormal immunoglobulin (Ig) levels, including an increased presence of autoreactive antibodies in the circulation of individuals with autism. As IgG is the predominant antibody isotype in circulation, we expected that an altered immune response could result in an abnormal IgG subclass profile in children with autism. We examined circulating plasma levels of IgG1, IgG2, IgG3, and IgG4 in 241 children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) study, a large epidemiologic case-control investigation, including 114 children who meet full criteria for autism disorder (AU), 96 typically developing control children (TD) from a randomly selected sample of the general population, and 31 children with developmental delays (DD). We report significantly increased levels of the IgG4 subclass in children with AU compared with TD control children (p=0.016) and compared with DD controls (p=0.041). These results may suggest an underlying immunological abnormality in AU subjects resulting in elevated IgG4 production. Further investigation is necessary to elucidate the relationship between immunological findings and behavioral impairments in autism.