Immune Response to Dietary Proteins, Gliadin and Cerebellar Peptides in Children with Autism

Abstract

The mechanisms behind autoimmune reaction to nervous system antigens in autism are not understood. We assessed the reactivity of sera from 50 autism patients and 50 healthy controls to specific peptides from gliadin and the cerebellum. A significant percentage of autism patients showed elevations in antibodies against gliadin and cerebellar peptides simultaneously. For examining cross-reaction between dietary proteins and cerebellar antigens, antibodies were prepared in rabbits, and binding of rabbit anti-gliadin, anti-cerebellar peptides, anti-MBP, anti-milk, anti-egg, anti-soy and anti-corn to either gliadin-or cerebellarantigen-coated wells was measured. In comparison to anti-gliadin peptide binding to gliadin peptide at 100%, the reaction of anti-cerebellar peptide to gliadin peptide was 22%, whereas the binding of anti-myelin basic protein (MBP), anti-milk, anti-egg and anti-soy to gliadin was less than 10%.Further examination of rabbit anti-gliadin (EQVPLVQQ) and anti-cerebellar (EDVPLLED) 8 amino acid (AA) peptides with human serum albumin (HSA) and an unrelated peptide showed no binding, but the reaction of these antibodies with both the cerebellar and gliadin peptides was greater than 60%. This crossreaction was further confirmed by DOT-immunoblot and inhibition studies. We conclude that a subgroup of patients with autism produce antibodies against Purkinje cells and gliadin peptides, which may be responsible for some of the neurological symptoms in autism.

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.…”

Theoretical aspects of autism: biomarkers—a review

“…Levels of antibodies directed against autologous cerebellar peptides, dipeptidyl peptidase IV, and/or gliadin were increased in the serum of autistic subjects (Vojdani et al, 2004a(Vojdani et al, , 2004b. Serum or plasma levels of other autoantibodies including those against glial filament and neurofilament proteins (Singh et al, 1997), and myelin basic protein were also increased (Singh et al, 1993).…”

Complementary Medicine Products Used in Autism - Evidence for Rationale

“…It is hypothesised that autoimmune disease in autism may lead to neurodevelopmental damage. Autoantibodies against proteins associated with the central nervous system (CNS) has been reported in some children with autism (Singh et al 1988;Plioplys et al 1994;Vojdani et al 2004). In recent studies, antibodies against the fetal brain have been detected in some mothers of children with autism; these antibodies have the ability to alter behavioural outcomes in the offspring of animal models (Enstrom et al 2009).…”