Overview Introduction How Could Vaccines Cause Damage? Early Studies on Vaccine Complications The DPT Vaccine DPT and Brain Damage DPT and Autism DPT and Vaccine-Induced Neuropathies Diagnosis of Post-Vaccinal CNS Pathology Vaccine-Induced Demyelination Auto-Immunity, Vaccines and Autism  ' Database of Vaccine Injury Vaccines and Mercury Origins of the Mercury Controversy Mercury Neurotoxicity Thimerosal and Neurotoxicity Is There a Link betwen Mercury Exposure and Autism? Ethylmercury and the DPT Vaccine Testing for Mercury Toxicity The MMR Vaccine MMR Vaccine and Autism MMR Vaccine and Other Complications Other Vaccination Concerns Concern About Vaccine Adjuvants Immunological Consequence of Vaccines Vaccination During Pregancy and Risks for Autism The Rubeola (Measles) Vaccine The Rubeola Vaccine, Measles and Autism The Risks of Not Vaccinating for Measles Conflict of Interest and Vaccine Development The Hepatitis B Vaccine Hepatitis B Vaccine: The Risks Hepatitis B: The Disease Available Data on the Safety of Hepatitis B Vaccines Information on Other Vaccines Polio Vaccine Pneumococcal Pneumonia Vaccine Hemophilus Meningitis Vaccine Appendix 1: Schedule for Routine Immunizations Appendix 2: Standards for Pediatric Immunization Practices Appendix 3: Decline of Number of Vaccine-Preventable Cases over Time Appendix 4: Childhood Immunizations The Burden of Suffering Description of Preventive Measures Evidence of Effectiveness Public Policy Considerations Recommendations of Other Groups Rationale Statement Recommendations of the American College of Preventive Medicine

V.K. Singh has studied autism as an autoimmune disorder for over fifteen years. He believes that up to eighty percent (and possibly all) cases of autism are caused by an abnormal immune reaction, commonly known as autoimmunity. The autoimmune process in autism results from a complex interaction between the immune system and the nervous system. He hypothesizes that an auto-immune reaction to basic brain structures, especially the myelin sheath, plays a critical role in causing the neurological impairments of patients with autism. He has suggested that an immune insult to developing myelin (after a natural infection or vaccination) causes "nicks" or small changes in the myelin sheath. These changes ultimately lead to life-long disturbances of higher mental functions such as learning, memory, communication, social interaction, etc.¹

A disease is sometimes referred to as "autoimmune" when the etiology and pathogenesis is not well known or established. Autoimmunity is an abnormal immune reaction in which the immune system becomes primed to react against body organs, and the end result is autoimmune disease. Several factors contribute to the pathogenic mechanism of autoimmune diseases. These illnesses are commonly believed to be triggered by infectious agents; further, they are generally linked to genes that control immune responses. They cause immune abnormalities of T lymphocytes (one type of white blood cell); they induce the production of autoantibodies; they involve hormonal factors; and they generally show a gender preference.

This is also the case with autism: several autoimmune factors have been identified in patients with autism, suggesting the pathogenetic role of autoimmunity in autism. Some generalities regarding the genetics and immunology of autism are below:

Autism displays increased frequency of genetic factors for immune responses, e.g., HLA, C4B null allele and extended haplotypes. Autism involves a gender factor, i.e., it affects males about four times more than females. Autism often occurs in conjunction with a family history of autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, etc. Autism also involves hormonal factors, e.g., secretin, beta-endorphin, etc. Autism shows an association with infectious agents, in particular, viruses. Autistic patients have immune abnormalities, especially those that characterize an autoimmune reaction in a disease. Autistic patients also respond well to immune therapies.

The linkage of vaccines to neurological disorders comes through the promotion of an auto-immune process, triggered by the virus present in the vaccine together with the adjuvant used to sensitize the body to this virus. Wild viruses have also been linked to autism. Certain viral infections can easily be acquired during fetal life, infancy or early childhood. They can enter the brain through the nasopharyngeal membranes or induce an autoimmune response against the brain, thereby altering the development of brain function.

Since autism is an early-onset disorder, usually diagnosed before the age of 30 months, it has been suggested that viruses might serve as teratogens (agents that cause developmental malfunctions) contributing to autism.

Earlier studies implicated congenital rubella virus (RV), simply because children with this infection also showed autistic behaviors. Moreover, several autistic children did not produce antibodies to rubella vaccine even after the repeated rubella immunization. Although the reason for this problem has not been investigated, Singh believes it due to a defect in T lymphocytes reducing their functionality. In support of this, RV-induced lymphocyte proliferation response in autistic children was only one-fourth of the response in normal children.

A few cases of autism have also been described among children with congenital cytomegalovirus (CMV). Interestingly, an autistic child with CMV responded favorably to treatment with transfer factor, but there was no follow-up to the study in which this was reported. Singh and co-workers conducted a study of IgG antibodies to CMV. They found no statistical difference between autistic children and normal children.² Simply put, this means that CMV is probably not related to autism.

Singh conducted a study of measles virus (MV) and human herpes virus-6 (HHV-6) in autism. This was done by two types of laboratory analysis: (a) virus antibody levels of MV and HHV-6; and (b) brain autoantibody titers in the same samples as those assayed for virus antibodies. This study showed that the virus antibody levels in the blood of autistic children were much higher when compared to normal children; and that the elevated virus antibody levels were associated with brain autoantibody titer. Interestingly, the viral antibody and brain autoantibody association was particularly true of MV antibody and MBP autoantibody (i.e., 90 percent of autistic children showed this association).

This observation led Singh to hypothesize that a measles virus-induced autoimmune response was a causal factor in autism, whereas HHV-6 via co-infection could also contribute to pathophysiology of the disorder. Although as yet unproven, Singh thinks it is an excellent working hypothesis to explain autism, and may also explain why some children show autistic regression after the measles-mumps-rubella (MMR) immunization. A small but significant proportion of children develop autism as a result of pre-or post-natal infections - for example, with rubella, cytomegalovirus, herpes simplex, HIV, and so on.³

William Shaw reports that he found none of the signs characteristic of known, inborn (genetic) metabolic disorders among children with autism and PDD (pages 31; 35-37; 68-9; 129). On pages 103-4 Shaw noted, "In several cases, electron microscopy has revealed live measles virus in the intestinal lining of children with the gastrointestinal abnormalities common in children with autism."

Since the brain is the affected organ in autism and other vaccine-induced neurological disorders, the autoimmune response will be directed against this organ. This response is commonly identified by certain autoimmune factors that have been identified in autistic children. The list includes brain-specific autoantibodies, viral antibodies, cytokine profile, immune activation markers, and antinuclear antibodies. Collectively, these are essential for identifying a brain-specific autoimmune response.

Brain autoantibody studies detect antibodies to two brain proteins - the myelin basic protein (MBP) and neuron-axon filament proteins (NAFP). The incidence of MBP antibody in the autistic population (70% positive) is over twenty times higher than that of the normal population (3% positive); hence, it serves as a primary marker of the autoimmune reaction in autism. In contrast, the incidence of NAFP antibody in autistic patients (55% positive) is only about twice that of normal controls (27% positive), making it a secondary marker of autoimmunity in autism.

Two immune activation markers or cytokines, namely interleukin-12 (IL-12) and interferon gamma (IFN-g), play key roles in the induction of autoimmune diseases, i.e., they initiate an autoimmune reaction. They are selectively elevated in autistic patients and should be measured as a sign of altered cellular autoimmunity - a function of Th-1 type white blood cells.

Virus serology measures levels of antibodies to measles (rubeola) virus (MV) and human herpes virus-6 (HHV-6). The antibody levels are elevated, which is a sign of a present infection, past infection, or reaction to measles-mumps-rubella (MMR) vaccine. The HHV-6 and measles viruses are etiologically-linked to autism because they are related to brain autoantibodies and demyelinating diseases.

Antinuclear antibodies (ANA) are non-specific antibodies often present in patients with autoimmune diseases. Approximately one-third of autistic children tested have positive titers of ANA. [Reference: V. Singh, 1992; unpublished data].

The induction of an auto-immune process against the central nervous system (particularly the myelin basic protein) may be the way that vaccines - coupled with their adjuvants - cause neurological damage, including seizures, autism, and encephalitis.⁴ Recently thirty-three autistic children (less than or equal to 10 years of age) were compared to controls which included 18 normal children (of the same ages), 20 children with idiopathic mental retardation (MR) of the same ages, 12 children with Down's syndrome (DS) of the same age, and 38 normal adults in the age range of 20 to 40 years.⁵

Antibodies to myelin basic protein were found in 19 of 33 (58%) sera from autistic children. In contrast, only 8 of 88 (9%) control sera were positive. Among these control sera, 3 of 20 (15%) sera were from MR children, 4 of 18 (22%) sera were from normal children, only one of 38 sera was from normal adults (25 to 40 years of age), but none of the 12 sera from the DS children showed this antibody positive reaction.

The authors suggested that the humoral, immune response to myelin basic protein (MBP) could be related in some way to mental retardation, since approximately 60% of autistic children had an IQ of 70 of lower. Seizure activity or antipsychotic drugs were not thought to relate to the production of anti-MBP, since there was neither the history of seizures nor the intake of antipsychotics (at least not at the time of blood drawing) among autistic or retarded children that were studied.

Immunological studies of autistic patients have revealed certain features that are also found in patients with other autoimmune diseases. There is a genetic predisposition for several autoimmune diseases⁶ , like grave's thyroid disease, rheumatoid arthritis, and insulin-dependant diabetes. Likewise, autism shows a greater concordance rate in monozygotic twins than in the normal population.⁷ Autism is also four to five times more prevalent in boys than in girls Ç a gender factor which is also seen in systemic lupus erythematosus (SLE), Grave's disease, and ankylosing spondylintis (though this is more common with women than men).

Triggering by microorganisms is thought to be an important feature of autoimmune diseases. Whether a similar event is associated with autism is not known but there are coincidental findings of congenital rubella⁸ and cytomegalovirus,^9,10 indicating prior exposure to these microbial agents. Certain soluble antigens of immunocyte activation are elevated in the sera of autistic children,¹¹ which is in concordance with similar findings in other autoimmune diseases, like SLE¹² and multiple sclerosis.¹³

Forty to fifty percent of autistic patients show signs of depressed immunity, including reduced lymphocyte proliferation by phytohemagglutinin, concanavalin A, and pokeweed mitogens^14,15,16 along with depression of the proportion of CD4+ T helper cells to suppresor-inducer (CD4CD45RA+) cells.^17,18,19 They also showed reduced numbers of CD2+ T cells, CD4+ cells, and CD4+CD45RA+ lymphocytes,²⁰ along with reduced B cells (CD20+) and a lower percentage of total lymphocytes than siblings and normal children.²¹

The level of blood values for female subjects appeared lower than those for males as compared to normal subjects of the same sex. While family and twin studies support a genetic component for autistic spectrum disorders, children with autism, also have increased eosinophil and basophil response to IgE-mediated reactions.²²

A cause and effect relationship between antibodies to myelin basic protein (MBP) and autism has not yet been definitively established. There may be many routes to autism, of which auto-immunity is only one. Nevertheless, the development of antibodies to MBP may be a major route through which vaccination contributes to autism.

Another possibility for post-vaccine related damage is delayed or incomplete myelination in the corpus callosum (the largest myelinated area of the brain), which has been suggested as a basis for auditory processing problems in some children with learning disabilities (LD).²³ Immunological assaults from wild virus infection or vaccine virus infection could theoretically result in poor myelination or abnormal function of the neuron-axon myelin.

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1. Singh VK. Autism, Autoimmunity and Immunotherapy: a Commentary, Autism Autoimmunity Project.
   
   
2. V. Singh, D. Schubert and R. Warren, 1992; unpublished data.
   
   
3. Cohen and Volkmar, eds., Handbook of Autism and Pervasive Developmental Disorders, 2nd edition, 1997: p. 398.
   
   
4. Singh VK. CD4+ Helper T Cell Depression in Autism. Immunology Letters, 1990; 25(4): 341-5.
   
   
5. Brain, Behavior, and Immunity 7, 97-103 (1993).
   
   
6. Shoenfeld, Y., & Isenberg, D. (1989). The genetic components in autoimmunity. In The Mosaic of Autoimmunity, chap. 5, pp. 169-228. Elsevier: Amsterdam.
   
   
7. Folstein, S., & Rutter M. (1988). Autism: Familial aggregation and genetic implications. J. Aut. Develop. Disord. 18, 3-30.
   
   
8. Chess, S. (1971). Autism in children with congenital rubella. J. Aut. Childh. Schizophr. 1, 33-47.
   
   
9. Ivarsson, S. A., Bjerre, I., Vegfors, P., & Ahlfors, K. (1990). Autism as one of several abnormalities in two children with congenital cytomegalovirus infection. Neuropediatrics 21, 102-103.
   
   
10. Stubbs, E.G. (1987). Does intrauterine cytomegalovirs plus autoantibodies contribute to autism? In L. Wing (Ed.), Aspects of Autism: Biological Research, Gaskell Psychiatry Series, pp. 91-101.
    
    
11. Singh, V. K., Warren, R.P., Odell, J.D., & Cole, P. (1991). Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. Clin. Immunol. Immunopath. 61, 448-455.
    
    
12. Huang, Y.P., Perrin, L.H., Miescher, P.A., & Zubler, R.H. (1988). Coorelation of T and B cell activites in vitro and serum IL-2 levels in systemic lupus erythematosus. J. Immunol. 141, 827-833.
    
    
13. Trotter, J.L., Clifford, D. B., Anderson, C. B., van der Veen, R. C., Hicks, B.C., & Banks, G. (1988). Elevated serum interleukin-2 levels in chronic progressive multiple sclerosis. N. Engl. J. Med. 318, 1206.
    
    
14. Singh, V. K., Fudenberg, H.H., Emerson, D., & Coleman, M. (1988). Immunodiagnosis and immunotherapy in autistic children. Ann. N.Y. Acad. Sci. 540, 602-604.
    
    
15. Stubbs, E.G. Crawford, M. L., Burger, D.R., & Vandenbark, A. A. (1977). Depressed lymphocyte responsiveness in autistic children. J. Aut. Childh. Schizophr. 7, 49-55.
    
    
16. Warren, R. P., Foster, A., Margretten, N. C., & Pace, N. C. (1986). Immune abnormalities in patients with autism. J. Aut. Dev. Disord. 16, 189-197.
    
    
17. Warren, R. P., Yonk, L. J., Burger, R.A., Cole, P., Odell, J. D., Warren, W. L., White, E., & Singh, V. K. (1990). Deficiency of suppressor-inducer (CD4 + Cd45RA + ) T cells in autism. Immunol. Invest. 19, 245-251.
    
    
18. Yonk, L. J., Warren, R. P., Burger, R. A., Cole, P., Odell, J. D., Warren, W. L., White, E., & Singh, V. K. (1990). CD4+ helper T cell depression in autism. Immunol. Lett. 25, 341-346.
    
    
19. Singh VK. Changes of Soluble Interleukin-2, Interleukin-2 Receptor, T8 Antigen, and Interleukin-1 in the Serum of Autistic Children. Clinical Immunology and Immunopathology, 1991; 61(3): 448-455.
    
    
20. Singh VK. Deficiency of Suppressor-inducer (CD4+CD45RA+) T Cells in Autism. Immunological Investigations, 1990; 19(3): 245-51.
    
    
21. Singh VK. CD4+ Helper T Cell Depression in Autism. Immunology Letters, 1990; 25(4): 341-5.
    
    
22. Trottier G. Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. Journal of Psychiatry and Neuroscience, 1999; 24(2): 103-15.
    
    
23. Musiek, F. E., Gollegly, K. M., & Baran, J. A. (1984). Myelination of the corpus callosum and auditory processing problems in children: theoretical and clinical correlates. Semin. Hearing 5, 231-241.