Most authorities agree that post-vaccine pathology of the central nervous system needs to be studied further.1 Among 30 Italian patients observed between April, 1994 and October, 1995, symptoms occurred after vaccination with Salk or Sabin polio vaccine, DT, measles, DPT, anti-tuberculosis, or Hepatitis-B vaccines. These symptoms included dermatitis, food allergies, constipation, and anal leakage. Demyelination has been described after immunization with hepatitis B vaccine.2 Loss of vision and eosinophilia has also been reported after hepatitis B vaccine.3
Montnari's patients came from various regions of Italy, all presenting with a clinical history of seizures occuring concomitantly with, or immediately after vaccinations. Patients whose symptoms were not referable to a vaccination were excluded. Patients were tissue typed for HLA (A, B, C) and HLA DR-DQ. Phenotypes were defined by a study of various immune functions: lymphocyte sub-populations, serum immunoglobulin content, sphericity of the antibodies to various viruses (CMV, EBV, HSV-1 and HSV-2, VZV). This phenotyping was related to several specific clinical pictures - patients who had earlier been diagnosed with epilepsy, myoclonic epilepsy, evolving epilepsy, epileptigenic encephalopathy, autism, West Syndrome, and Angelman's Syndrome. All these patients had presented with the first symptoms shortly after receiving prophylactic vaccination.
Patients' first symptoms were convulsions, high fever, or diarrhea immediately following vaccination. Progressive clinical deterioration occurred after the second dose of the vaccine. Children were mostly from 3 to 9 months old. No patients had metabolic diseases. Chromosomal mapping was negative. Encephalic TAC and RMN tests were negative also. EEG performed at first appearance of the symptomatology gave a negative result in 92% of the patients. Serologic
investigations for herpetic virus (IgG and IgM) were positive in all for IgG and negative in all for IgM, leading to an estimate of IgG seropositivity for Epstein-Barr virus of 73.8%; for cytomegalovirus, of 71.4%; for Herpes Simplex virus, of 47.6%; and for Varicella-Zoster Virus, of 21.4%.
All patients observed showed sideremia with reductions in IgA and IgG, and a slight increase of SGOT and SGPT. None of the patients had maternally transmitted viral encephalopathy. The vegetative and relational life was quite normal in all patients prior to administration of the first dose of vaccine.
The patients were subjected to HLA tissue typing (A, B, and C), and serologic HLA DR-DQ, with the aim of checking a possible correlation with the emergence ofCNS pathology, and these antigens indicate a possible autoimmune immunogenetic basis for the demyelination process.
The HLA-A3 antigen was increased among patients compared to Italian normal controls (43.3% vs. 25%, p = 0.04, after statistical correction) as was the HLA-DR7 antigen (48.3% vs. 24.14% P = 0.007, after statistical correction). The presence of A3 and/or DR7 was observed in 22 of 30 (73.3%) of the patients. The presence of these antigens were thought to indicate a possible autoimmune immunogenetic basis for the demyelinating process.4
HLA system alleles have an elevated genetic polymorphism and are inherited as autosomal dominant characteristics. The combination of the alleles of various loci in the same chromosomes has been defined as the haplotype or complex gene, and the complexity of the HLA region demonstrates, besides a thousand different possible haplotypes, also the problems: of molecular resemblance5 , of discriminating between self- and non-self-antigens, and of determining the function of the Class 2a CMI molecules; any interference with the process of presentation of the antigen can predispose to an autoimmune disease.
Alterations which do not occur can be due to the action of viral agents which compromise the specific immune response because of their resemblance to the "self" tissue antigens. The consequence is persistence of the infective agents and a tendency to provoke, through a marked reaction, induction of an autoimmune disease. This can present in conditions of marked reactivity to some viruses and to myelin antigens.
A study of the disease associated with genes of the HLA system has shown that this genetic complex can be responsible for a particular genetic susceptibility, predisposing to various diseases characterized predominantly by immune-system pathogenesis. The observation that many vaccines use thimerosal as a preservative, for which we do not have clear dose-response relationships and whose toxic effects take the form essentially of neurologic symptoms, not the
least of which are symptoms of the purine pathway of the innervation of the digestive tube, leads us to consider that in 66% of cases there was obstinate constipation and in 31% there was proctic symptomatology with emission of mucus and blood.
All the patients observed presented various physical problems. The various types of CNS pathology could be due to a delatentization of preexisting autoimmune damage by viral DNA. It has been observed that the "cleaner" the species, from the virologic or microbiologic point of view, the more likely it is to present autoimmune conditions of the CNS and other apparatuses.
The results indicated that autoimmune pathology is more frequent in countries where vaccination is more widespread, i.e., in countries defined as "clean." With this study, and with the individualization of alleles such as A3 and DR7, in the presence of viral DNA, it would be possible to define the subjects at risk of an autoimmune pathology from vaccination.
The action of thimerosal used as an excipient in vaccines, and whose toxicity is independent of the dose administered, could demonstrate the possibility of changes in the amino acids of the molecules which preserve the antigen. This type of study could even be utilized to individualize the etiopathogenesis of other types of autoimmune pathology.
