Autoimmunity and Inflammation

 

Neurosci Lett. 2004 Jan 23;355(1-2):53-6.

Prevalence of serum antibodies to caudate nucleus in autistic children.

Singh VK, Rivas WH.

Department of Biology, Biotechnology Center Building, Utah State University, 4700 Old Main Hill, Logan, UT 84322-4700, USA. singhvk@cc.usu.edu

Autism may involve autoimmunity to brain. We studied regional distribution of antibodies to rat caudate nucleus, cerebral cortex, cerebellum, brain stem and hippocampus. The study included 30 normal and 68 autistic children. Antibodies were assayed by immunoblotting. Autistic children, but not normal children, had antibodies to caudate nucleus (49% positive sera), cerebral cortex (18% positive sera) and cerebellum (9% positive sera). Brain stem and hippocampus were negative. Antibodies to caudate nucleus were directed towards three proteins having 160, 115 and 49 kD molecular weights. Since a significant number of autistic children had antibodies to caudate nucleus, we propose that an autoimmune reaction to this brain region may cause neurological impairments in autistic children. Thus, the caudate nucleus might be involved in the neurobiology of autism.

Abstract

 

Journal of Allergy Clin Immunol 109 (1):S232, 2002 (January).  Vijendra K Singh

Courtney Nelson
Utah State University,
Logan, UT

 Immune factors such as autoimmunity may play a causal role in autism. We recently showed that many autistic children have autoantibodies to brain myelin basic protein (MBP) as well as elevated levels of measles virus antibodies. To extend this research further, we conducted a serological study of measles virus (MV), mumps virus (MuV), rubella virus (RV), cytomegalovirus  (CMV), human herpesvirus-6 (HHV-6), measles-mumps-rubella (MMR), diptheria-pertussis-tetanus (DPT), diptheria-tetanus (DT) and  hepatitis B (Hep B) and studied correlations with MBP autoantibodies. Antibodies were assayed in sera of autistic children (n=125) and normal children (n=92) by ELISA or immunoblotting methods. We found that autistic children have significantly (p=0.001) higher than normal levels of MV and MMR antibodies whereas the antibody levels of MuV, RV, CMV, HHV-6, DPT, DT or  Hep B did not significantly differ between autistic and normal children. Immunoblotting analysis showed the presence of an unusual MMR antibody in 60% (75 of 125) of autistic children, but none of the 92 normal children had this antibody. Moreover,  by using MMR blots and monoclonal antibodies, we found that the specific increase of MV antibodies or MMR antibodies was related to measles hemagglutinin antigen (MV-HA), but not to mumps or rubella viral proteins, of the MMR vaccine. In addition, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a causal association between MMR and brain autoimmunity in autism. Stemming from this evidence, we suggest that an "atypical" measles infection in the absence of a rash but with neurological symptoms might be etiologically linked to autoimmunity in autism. (Supported by grants from the James Dougherty Jr Foundation, Unanue Foundation, Lettner Jr Foundation, Autism Autoimmunity Project and Autism Research Institute)

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Nutr Neurosci. 2004 Jun;7(3):151-61.

Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism.

Vojdani A, O'Bryan T, Green JA, Mccandless J, Woeller KN, Vojdani E, Nourian AA, Cooper EL.

Section of Neuroimmunology, Immunosciences Lab., Inc., 8693 Wilshire Blvd., Ste. 200, Beverly Hills, California 90211, USA. drari@msn.com

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 cerebellar-antigen-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 cross-reaction 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.

Abstract

 

Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):189-99.

Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.

Vojdani A, Pangborn JB, Vojdani E, Cooper EL.

Lab. Comparative Immunology, Dept. Neurobiology, UCLA Medical Center, Los Angeles, CA, USA. DrAri@msn.com

Similar to many complex autoimmune diseases, genetic and environmental factors including diet, infection and xenobiotics play a critical role in the development of autism. In this study, we postulated that infectious agent antigens such as streptokinase, dietary peptides (gliadin and casein) and ethyl mercury (xenobiotic) bind to different lymphocyte receptors and tissue enzyme (DPP IV or CD26). We assessed this hypothesis first by measuring IgG, IgM and IgA antibodies against CD26, CD69, streptokinase (SK), gliadin and casein peptides and against ethyl mercury bound to human serum albumin in patients with autism. A significant percentage of children with autism developed anti-SK, anti-gliadin and casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies. These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific. Immune absorption demonstrated that only specific antigens, like CD26, were capable of significantly reducing serum anti-CD26 levels. However, for direct demonstration of SK, gliadin, casein and ethyl mercury to CD26 or CD69, microtiter wells were coated with CD26 or CD69 alone or in combination with SK, gliadin, casein or ethyl mercury and then reacted with enzyme labeled rabbit anti-CD26 or anti-CD69. Adding these molecules to CD26 or CD69 resulted in 28-86% inhibition of CD26 or CD69 binding to anti-CD26 or anti-CD69 antibodies. The highest % binding of these antigens or peptides to CD26 or CD69 was attributed to SK and the lowest to casein peptides. We, therefore, propose that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules. In conclusion, this study is apparently the first to demonstrate that dietary peptides, bacterial toxins and xenobiotics bind to lymphocyte receptors and/or tissue enzymes, resulting in autoimmune reaction in children with autism.

Abstract

 

Pediatrics. 2003 Nov;112(5):e420.

Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders.

Sweeten TL, Bowyer SL, Posey DJ, Halberstadt GM, McDougle CJ.

Department of Psychiatry, Indiana University School of Medicine, and James Whitcomb Riley Hospital for Children Indianapolis 46202-4800, USA.

OBJECTIVES: Increased prevalence of familial autoimmune disease is a common finding among probands with various autoimmune disorders. Autistic disorder (autism) is a highly genetic disorder with known immune and immunogenetic abnormalities. Previous research has found an increased frequency of autoimmune disorders in families with autistic probands. We further investigated this association by determining the frequency of autoimmune disorders in families that have probands with pervasive developmental disorders (PDDs), including autism, compared with 2 control groups. METHODS: Three well-defined study groups, including 1) families that have a child with a PDD, 2) families that have a child with an autoimmune disorder, and 3) families with a healthy control child, constituted the sample. A questionnaire inquiring about which first- and second-degree family members had received a diagnosis of having specific autoimmune disorders was completed by 101 families in each group. RESULTS: The frequency of autoimmune disorders was significantly higher in families of the PDD probands compared with families of both the autoimmune and healthy control probands. Autoimmunity was highest among the parents of PDD probands compared with parents of the healthy control subjects. Hypothyroidism/Hashimoto's thyroiditis and rheumatic fever were significantly more common in families with PDD probands than in the healthy control families. CONCLUSIONS: Autoimmunity was increased significantly in families with PDD compared with those of healthy and autoimmune control subjects. These preliminary findings warrant additional investigation into immune and autoimmune mechanisms in autism.

Abstract

 
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