Is autism an autoimmune disease?
Introduction
The autistic spectrum disorders (ASD) are complex developmental disorders that are characterized by impairments in social interaction, deficits in communication and stereotyped patterns of behavior [1]. ASD describes a range of conditions including autism and Asperger's syndrome, in which, for the majority of cases the cause of remains unknown. So far, unequivocal evidence for a genetic association with ASD has yet to be established, with the most likely genetic models predicting multiple and weak gene interactions of 15 or more. Equally, ASD has been linked with environmental factors such as congenital rubella infection, anticonvulsants and antiemetics taken during pregnancy, perinatal hypoxia and postnatal infections such as encephalitis [2], [3]. Various genetic, prenatal and early postnatal environmental or biochemical factors have been implicated in ASD, but neither a definitive pattern of its etiology nor its pathophysiology has emerged to date.
Section snippets
The neuroimmune system in ASD
Systemic immunologic aberrations in ASD have been linked with both autoimmunity, describing antibodies reactive for central nervous system (CNS) proteins with the potential for neuronal tissue destruction, and with dysfunctional immunity such as abnormalities or deficits of function in immune cell subsets. The relationship between the various immune abnormalities that have been reported in individuals with ASD and the development of neurologic changes is not yet clear. There has been
Autoimmunity in ASD
The first suggestion that autoimmunity may be etiologically important in autism was noted in a case report in 1971 describing an autistic child with a strong family history of autoimmune disorders [11]. Common genes may contribute to a number of different autoimmune states in families [12], and immune dysfunction and brain development may be governed by similar genes (e.g., MHC third hypervariable region sequences 1 and 2, which have been associated with both autism and rheumatoid arthritis [13]
The role of xenobiotics in autism
Recently, it has been hypothesized that environmental exposure to various xenobiotics may contribute to ASD etiology either through direct or indirect effects on the immune system and/or the developing CNS. A variety of interactions among environmental agents, immune system dysfunction and ASD can be envisioned. The neuropathology of ASD may be induced and/or exacerbated by infectious agents or other toxicants as a direct consequence of activation of the immune system. Neurotoxicity may occur
Summary
In conclusion, numerous world-wide studies have demonstrated immunological abnormalities in children with ASD. These include the presence of autoantibodies to several antigens pertinent to the nervous system. However, as yet, no definitive autoantibody pattern in ASD has emerged. Admittedly, ASD encompasses a broad spectrum of behavioral anomalies and as such several sub-phenotypes may be represented. In addition, the presence of autoantibodies in the serum of these patients may be a secondary
Take-home messages
- •
Patients show evidence of immune dysregulation.
- •
Autoantibodies have been described in patients with autism to brain antigens.
- •
There is an increased incidence of autoimmune disease in the families of patients with autism.
Acknowledgement
This work was supported in part by grants from the UC Davis MIND Institute and NIEHS 1 P01 ES11269-01; EPA Log Number HQ-R-000; Visceral Charity, UK.
References (40)
- et al.
Prevalence of pervasive developmental disorders in the British nationwide survey of child mental health
J. Am. Acad. Child Adolesc. Psychiatry
(2001 (Jul)) - et al.
Strong association of the third hypervariable region of HLA-DR beta 1 with autism
J. Neuroimmunol.
(1996 (Jul.)) - et al.
Circulating autoantibodies to neuronal and glial filament proteins in autism
Pediatr. Neurol.
(1997 (Jul.)) - et al.
Antibrain antibodies in infantile autism
Biol. Psychiatry
(1988 (Mar. 15)) - et al.
Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders
J. Pediatr.
(1999 (May)) - et al.
Prevalence of serum antibodies to caudate nucleus in autistic children
Neurosci. Lett.
(2004 (Jan. 23)) - et al.
Antibodies to myelin basic protein in children with autistic behavior
Brain Behav. Immun.
(1993 (Mar.)) - et al.
Autoantibody repertoires to brain tissue in autism nuclear families
J. Neuroimmunol.
(2004 (Jul.)) - et al.
A Sensitive ELISA for glial fibrillary acidic protein: application in CSF of children
J. Neurosci. Methods
(1992 (Sep.)) - et al.
Cytokines in brain development and function
Adv. Protein Chem.
(1998)