In this perspective we defined four groups of individuals who might be susceptible to develop vaccination-induced ASIA: patients with prior post-vaccination autoimmune phenomena, patients with a medical history of autoimmunity, patients with a history of allergic reactions, and individuals who are prone to develop autoimmunity (having a family history of autoimmune diseases; asymptomatic carriers of autoantibodies; carrying certain genetic profiles, etc.).
Autistic children with a family history of autoimmunity (45%) had significantly higher frequency of serum anti-ds-DNA antibodies (48.9%) than patients without such a history (21.8%), P=0.008. There was a significant positive association between the seropositivity of anti-ds-DNA antibodies and ANA (P<0.001). In conclusion, anti-ds-DNA antibodies and ANA were found in the sera of a subgroup of autistic children. However, replication studies of larger samples are warranted to validate whether these antibodies are a mere association or have a pathogenic role in some autistic children.
Conclusion: Fractures, retinal and subdural haemorrhages and encephalopathy in children – is an autoimmune response to antigenic stimulation in a genetically susceptible individual. Common antigens are the mandated vaccines, viral bacterial and parasitic infections.
Vaccines have shown to cause a large number of cases of type 1 diabetes in both a prospective clinical trail as well as in animal toxicity studies . The pathophysiology is believed to involve vaccine induce macrophage activation, especially by aluminum adjuvants and complex polysaccharides, and resulting interleukin 1, interleukin 6, and TNF production. It is the belief of the author, based in part on the data present in this manuscript that the epidemics of type 1 diabetes and autoimmune autism are more likely than not to share the same etiological cause
Systemic autoimmunity appears to be the inevitable consequence of over-stimulating the host's immune ‘system’ by repeated immunization with antigen, to the levels that surpass system's self-organized criticality.
Based on this and other epidemiologic considerations, we had suggested that genetic factors would account for only a smaller percentage (≤10%) of autism cases, whereas the remaining, larger percentage (≥90%) of cases would be sporadic due to nongenetic factors.4 The sporadic form might be acquired from exposure to environmental factors such as viruses, vaccines, or chemical toxins and other unknown factors. In this article, the author summarizes his laboratory research to date and reviews scientific data that lend credibility to a virus-induced autoimmune mechanism of pathogenesis for autism....
We postulated that a virus-induced immune assault might cause “nicks” or subtle changes in the myelin sheath.2,4,10 An autoimmune reaction to the developing myelin sheath could ultimately lead to lifelong impairments of higher brain functions, such as speech, language, communication, and social interaction as well as other neurologic symptoms that are commonly exhibited by children with autism....
According to this NAI model, a viral infection (foreign antigen) could trigger an autoimmune response by activating antigen-presenting cells (macrophages or dendritic cells) that, via interleukin-12 (IL-12) induction, would activate T lymphocytes. As depicted in FIGURE 1, the viral infection appears to be a measles infection, possibly resulting from exposure to the measles-mumps-rubella (MMR) vaccine, but it could also be a latent or mutant measles strain....
T lymphocytes would be activated via production of interferon-γ (IFN-γ) and would change the cell permeability at the blood-brain barrier. This is because IFN-γ is the only known, naturally occurring molecule that induces the expression of Class I MHC antigens on the blood-brain barrier to cause permeability changes.14..
After crossing the blood-brain barrier, the Th1 cells could recognize antibrain antibodies (anti-myelin basic protein [MBP]) that would be produced by autoantigen MBP-primed B lymphocytes and then circulate in the brain. Then, owing to their specificity for myelin sheath, the anti-MBP antibodies by themselves, or by interaction with antigen-specific T lymphocytes, could cause cell damage to oligodendrocytes, the myelin-synthesizing cells in the CNS. Consequently, the function of the oligodendrocytes would be altered to produce abnormal myelin sheath during brain development.
The entire cascade of events leading to a neuroautoimmune response would be responsible for abnormal neurodevelopment—in particular, the functionality of neural circuits or neural pathways would most likely be disrupted. Since the myelinated neuron-axon fibers have a specific regional distribution in the brain, the overall outcome would result in neurologic and behavioral manifestations that are characteristic of autism/ASD...
Alternatively, in the absence of highly specific brain autoantibodies (anti-MBP), the Th1 cells could interact with astrocytes and/or microglia to produce neuroinflammation, which would lead to only nonspecific tissue damage. Thus, the phenotypic expression of autistic behaviors would be the result of subtle anatomic changes in the brain myelin sheath.
There is evidence for both systemic inflammation20 and brain inflammation in autism.25,26 As summarized elsewhere,2 anatomic and morphologic changes have been found in the white matter of brains of children with autism. Afterward, the white matter changes were also found by magnetic resonance imaging (MRI).27,28 In this regard, we postulated that autoimmunity to brain myelin could possibly induce developmental changes of white matter, which is composed of predominantly myelinated nerve fibers. Although this is a good possibility, other biochemical mechanisms should also be explored...
What triggers autoimmunity in autism is not known, but there is scientific evidence to suggest that measles virus might be a culprit; however, other infectious agents should also be examined. Although autoimmunity is commonly triggered by viral infections, other environmental factors, such as heavy metals (eg, mercury), can also induce an autoimmune response in animal models. However, there is no human study that supports the idea of autoimmunity in autism from exposure to heavy metals like mercury.42,43 Based on these considerations, we explored 2 possibilities in autism: (1) virus-induced autoimmune reaction, and (2) heavy metal (mercury)–induced autoimmune reaction. They are described in the following section...
TABLE 1Immune abnormalities in autistic children
1. In autism, microbial associations of certain viruses such as measles, rubella, and cytomegalovirus (CMV) have been shown.21,29,30
2. Autistic children show a hyperimmune antibody response that recognizes hemagglutinin antigen (HA) of the measles virus, measles vaccine, and measles-mumps-rubella (MMR) vaccine, which abnormally correlates with autoantibodies to myelin basic protein (MBP).21-24
3. Autism displays increased frequency of immune response (IR) genes, for example HLA antigens, C4B null allele, haplotype B44-SC30-DR4, HLA-C, and HLA-B1.31
4. Autistic patients have impaired humoral immunity, as shown by IgA deficiency; increased IgG3, and circulating antinuclear antibodies and immune complexes.4,32
5. Autistic children have a deficiency of cellular immunity, as demonstrated by decreased lymphocyte counts, low T helper cell (CD4+) counts, reduced natural killer (NK) cell counts, suppressed mitogen-induced lymphocyte proliferation, and reduced function of NK cells.32-47
6. Autism involves a gender factor, affecting males about 4 times more often than females.
7. Autism often accompanies a family history of autoimmune diseases, for example, multiple sclerosis, rheumatoid arthritis, and type 2 diabetes mellitus.11
8. Autism involves hormonal factors, eg, secretin, beta-endorphin, etc.2-4
9. Autistic patients have brain-specific autoantibodies; these are specific to brain MBP, which is a candidate autoantigen in autism.4,10,17
10. Autistic children show an autoimmune reaction to specific proteins of the caudate nucleus, implying a pathogenic role for this particular brain region in autism.17
11. Autoantibodies to other brain antigens, like neuron-axon filament proteins (NAFP), serotonin receptor proteins, and galactocerebrosides, are also found but they are not specific to autism because they are also found in many normal children.2,18,19
12. Autistic patients show immune activation as reflected by T-cell activation and elevation of autoimmunity-specific cytokines.3,9,38
13. Autistic patients respond well to autoimmune therapy with oral autoantigen, transfer factor, and intravenous immunoglobulin.2-4,8,32,39-41
14. Autistic children have acute-phase systemic inflammation, as demonstrated by elevated levels of serum C-reactive protein (CRP) and S100 proteins, which most likely precedes inflammation of the brain.20
15. Autistic children have normal levels of metallothionein (MT) protein, and antibodies to MT (anti-MT) are also in the normal range.42,43
The presence of MBP autoantibodies in both the blood and CSF suggests that the autoimmune reaction is also localized in the brains of autistic children. Furthermore, the presence of MMR antibodies in 3 of 10 CSF specimens (TABLE 4) is a highly positive sign of MMR-acquired measles infection in the brain of these autistic children. Unlike the highly select anti-MBP and anti-MMR immune markers, the nonspecific anti-NAFP marker was not found in CSF specimens. Thus, there is a positive correlation between MMR antibodies and MBP autoantibodies in autistic children, suggesting an etiologic link of MMR-derived measles virus to autoimmunity in autism.22-24
Collectively, these findings suggested an etiologic link between the MMR vaccine and autoimmunity in autism. As far as we know, this is the first study of its kind to examine associations between a viral factor (virus serology) and an autoimmune factor (brain autoantibodies) in a medical condition (autism/ASD) in which autoimmunity appears to be the core of the problem. Evidently, our study might also represent a novel mechanism by which the so-called autistic regression post-MMR vaccination might be explained in at least some children with ASD.22
Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).
Exposure to HiB immunization is associated with an increase risk of IDDM