Circulating autoantibodies to neuronal and glial filament proteins in autism

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

“…This is consistent with the findings of Singh et al [87,88] of elevated glutamate and inflammatory cytokines in the blood, CSF, and brain of autistic children. Hamberger et al [89] described four patients with Rett´s syndrome who had significantly elevated CSF glutamate levels, thought to originate from microglia.…”

Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

“…Within the adaptive immune response, elevated levels have been reported for both T H 1 cytokines, commonly seen in autoimmune disorders (Singh, 1996), and T H 2 cytokines, as seen in atopic diseases (Gupta, Aggarwal, & Heads, 1998). Elevated serum immunoglobulins (Croonenberghs et al, 2002b) and autoantibodies to neuronal elements (Singh, Warren, Averett, & Ghaziuddin, 1997) have also been reported in children with autism. In addition, Comi et al reported that 66% of children with autism had at least one relative with an autoimmune disorder, compared to 50% of normally developing controls (Comi, Zimmerman, Frye, Law, & Peeden, 1999).…”

“…While there is evidence to support ASD as an autoimmune phenomenon which is commonly associated with a cell-mediated, T H 1 response (Comi, Zimmerman, Frye, Law, & Peeden, 1999;Singh, Warren, Averett, Ghaziuddin, 1997;Sweeten, Bowyer, Posey, Halberstadt, & McDougle, 2003) there is also evidence that the disorder is associated with an allergic (T H 2) immune response (Lucarelli, et al, 1995;Gupta, Aggarwal, Rashanravan, & Lee, 1998), or that ASD is associated with general dysregulation of the immune system (Gupta, Aggarwal & Heads, 1996;Jyonouchi, Sun, & Le, 2001). These conflicting results may be due in part to the underlying heterogeneity within ASD, a diagnosis based on observable clinical and historical findings.…”

Immune Dysfunction in Autism: A Pathway to Treatment

“…PTEN is a major upstream regulator in the mTOR pathway, and mutations in this protein are associated with higher rates of ASD. 46 In an animal model with PTEN-deficient cells, Foxp3, a putative controller for the generation of regulatory T-cells, was found to be downregulated, 88 leading to decreased number of cells that suppress immune responses and thus favoring immune dysfunction, activa- 63 (1993) Myelin basic protein (MBP) Positive Singh et al 64 (1997) Neuron-axon acidic protein (NAFP); glial fibrillary acidic protein (GFAP) Positive Singh et al 65 (1998) Myelin basic protein (MBP); neuron-axon filament Positive Evers et al 66 (2002) Heat shock protein 90 (HSP90) Positive Vodjani et al 67 (2004) Gliadin; cerebellar peptides; heat shock protein 60 (HSP60) Positive Singh et al 68 (2004) Caudate nucleus; cerebral cortex; cerebellum Positive Singh et al 69 (2004) Nucleus and laminin Negative Silva et al 20 (2004) Unknown ϳ20 kDa protein Positive* Connolly et al 70 69 found a positive finding for a ϳ20 kDa protein, but determined it not to be MBP. (1998) tion, or both.…”