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Could Autism be an Autoimmune disease? PDF Print E-mail

 

1. Autism is highly associated with a family history of certain autoimmune diseases.

2. Several autoimmune diseases associated with autism are linked to the serotype HLA-DR4

  • Type 1 Diabetes and Rheumatoid arthritis are associated with HLA-DR4 (and other HLA types too): http://en.wikipedia.org/wiki/HLA-DR4
  • Postpartum thyroiditis is associated with HLA-DR4: “The DR4 antigen frequency was found to be even higher, 69.0% (relative risk = 4.36; P less than 0.001), among the 29 women who developed hypothyroidism in the postpartum period.” http://www.ncbi.nlm.nih.gov/pubmed/3871091

3. Autism is also highly associated with HLA-DR4:

  • Results of HLA typing indicated that mothers and their sons in the geographically defined group had a significantly higher frequency of DR4 than normal control subjects (odds ratio = 5.54, 95% confidence interval = 1.74-18.67 and odds ratio = 4.20, 95% confidence interval = 1.37-13.27, respectively).” http://www.ncbi.nlm.nih.gov/pubmed/17074598?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=12
  • “We have evaluated possible contributions of HLA-DRB1 alleles to autism spectrum disorder (ASD) in 103 families of Caucasian descent. The DR4 allele occurred more often in probands than controls (0.007), whereas the DR13,14 alleles occurred less often in probands than controls (p = 0.003). The transmission disequilibrium test (TDT) indicated that the ASD probands inherited the DR4 allele more frequently than expected (p = 0.026) from the fathers.” http://www.ncbi.nlm.nih.gov/pubmed/12039413
  • “We previously reported that the complement C4B null allele appears to be associated with infantile autism. Since the C4B null allele is known to be part of the extended or ancestral haplotype [B44-SC30-Dr4], we investigated the incidence of [B44-Sc30-DR4] in 21 autistic children and their parents. This extended haplotype was increased by almost six-fold in the autistic subjects as compared with healthy controls. http://www.springerlink.com/content/n62331k80867817l/
  • Certain HLA-DR4 alleles (DRB1*0401 and DRB1*0404) are associated with autism:  “The HVR-3 of DRb1*0401 or the shared HVR-3 alleles DRb1*0404 and DRb1*0101, was expressed on extended haplotypes in 23 of 50 (46%) autistic subjects as compared to only 6 of 79 (7.5%) normal subjects.”  http://enabling.org/ia/celiac/aut/hla-war2.html
  • The HLA-DR4 allele DRB1*0401, mentioned in the above study, is associated with autism, MS, and many autoimmune disorders also associated with autism:  “DRB1*0401 is associated with multiple sclerosis[11], rheumatoid arthritis[12], type 1 diabetes[13][14], lyme disease induced arthritis”  http://en.wikipedia.org/wiki/HLA-DR4

4. Autism may also be an autoimmune disease of some type:

”Numerous studies show an autoimmune process caused by genetic and environmental factors contributes to autism. This is evidenced by the prevalence of several different autoantibodies in children with autism.”

  • Antibodies against Myelin Basic protein:
    • “Autoimmunity to myelin basic protein, the protein targeted in multiple sclerosis, is suspected of playing a causal role in autism. An unusual variant of measles-mumps-rubella antibodies are also seen in 60 percent of children with autism. More than 90 percent of autistic children with this variant had antibodies to myelin basic protein, suggesting a strong link between the measles-mumps-rubella vaccine and autism. A strong autoimmune reaction, particularly to the measles component of the vaccine, might be related to the pathogenesis of autism.” http://autoimmunedisease.suite101.com/article.cfm/autoimmune_autism
  • Antibodies against Encephalon (the brain):
    • “Ninety six percent of the autistics with anti-HSV antibodies also had anti-encephalon antibodies”
    • “The proportion of autistics with anti-encephalon IgG antibodies (77% anti-amygdala, 70% anti-caudate nucleus, 47.5% anti-cerebellum y anti-brain stem, 45% anti-hippocampus, 40% anti-corpus callosum and 17,5% anti-cortex) was significantly greater than that of controls (10% anti- amygdala y 5% anti- cerebellum) and was directly related to the severity of the autism.” http://www.medscape.com/medline/abstract/19961054

5. Vaccines can trigger autoimmune diseases in groups with a genetic susceptibility for autoimmune disease. So, could HLA-DR4, (or more specifically, the DR4 alleles DRB1*0401 and DRB1*0404 and/or the haplotype B44-Sc30-DR4), be a risk factor for vaccine-induced regressive autism?

  • If so, the same strategy proposed below that is intended to protect susceptible groups from developing vaccine-induced autoimmune diseases could also be applied to preventing vaccine-induced regressive autism: