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Comment by
Harris L. Coulter Ph.D:
This is, to my knowledge, the first
investigation to find biochemical markers of vaccine damage. It has not
yet been published but deserves publication.
This study should also have an impact on HLA typing, since it shows that
vaccinations can have an effect on the individual's HLA type (i.e., that
it is not necessarily congenital).
Role of Immunogenetics in the Diagnosis of
Postvaccinal CNS Pathology
By: Massimo Montinari*,
Biagio Favoino**, and Angela Roberto*** Dept. Of Pediatric Surgery,
University of Bari
Tissue Typing and Organ Transplantation Service, Bari Hospital and
Polyclinic - Virology Outpatient Clinic. Bari Hospital and Polyclinic.
Presented in Naples, May 9, 1996, under the auspices of the Associazione
per la Libera Universita Internazionale de Medicina Omeopatica "Samuel
Hahnemann" (LUIMO).
Resume
This study involves observations of 30 patients with post-vaccinal
pathology of the central nervous system and other systems where the first
symptoms appeared concomitantly with, or immediately after, administration
of a vaccine. All patients were subjected to serologic testing for herpes
virus (IgG and IgM) and to HLA (A, B, C) and HLA-DR-DQ tissue typing to
see if there was any correlation between the emergence of CNS pathology
and these various antigens, thus to show a possible autoimmune-type
immunogenetic basis for demyelination processes. Statistical comparison
with the Italian population used as controls revealed an increase in the
HLA-A3 and HLA-DR7 antigens. The presence of A3 and/or DR-7 was observed
in 22/30 (73.3%) of the patients.
Key words
Post-vaccinal pathology; HLA system; autoimmune pathology of the CNS.
Introduction
Post-vaccinal pathology of the central nervous system (CNS) is a topic
deserving further investigation. In fact, our own experience with 30
patients of Italian nationality, observed between April, 1994 and October,
1995, shows that clinical signs of CNS pathology -- associated with
dermatitis, food allergies, constipation, and leaking from the anus --
emerged concomitantly or immediately after vaccination with the Salk or
Sabin polio vaccine, DT, measles, DPT, anti-tuberculosis, or Hepatitis-B
vaccines.
The hypothesis of Herroelen, J. De Keyser, and G. Ebinger on "CNS
demyelination after immunization with recombinant hepatitis-B vaccine"
(Lancet, 338, November 9, 1991, 1174-1175), as verified by A.P. Brezin, M.
Lautier-Frau, M. Hamadani, and O. Rogeaux in their article, "Loss of
Vision and Eosinophilia after Recombinant Hepatitis-B Vaccine" (Lancet,
Italian Edition, April, 1994), suggests the need for a clinical
revaluation and a critical look at all the patients observed up to now in
Italian and European clinical centers.
Methods
The patients examined by us came from various regions of Italy, and all
presented with a clinical history of convulsions concomitantly with, or
immediately after, prophylactic vaccinations. We excluded from the study
all patients observed by us whose clinical history was not referable to a
vaccination. All the patients were subjected to tissue typing for HLA (A,
B, C) and HLA DR-DQ with the aim of defining the relative immunogenetic
order. The phenotype was defined by a study of various immune functions:
lymphocyte subpopulations, serum immunoglobulin content, sphericity of the
antibodies to various viruses (CMV, EBV, HSV-1 and HSV-2, VZV).
This allowed us to relate these data to specific clinical pictures --
patients who had earlier been diagnosed with epilepsy, myoclonic epilepsy,
evoving epilepsy, epileptigenic encephalopathy, autism, West Syndrome, and
Angelman's Syndrome. All the patients had presented with the first
symptoms shortly after receiving the prophylactic vaccination or somewhat
later.
The first symptoms were convulsions, very high fever, or diarrhoea
immediately following a compulsory vaccination. The parents had told their
physicians about this; then, after taking EEGs and visiting
neuropsychiatric specialists or pediatricians without getting any
satisfaction, the physicians had administered the recall shots of the
vaccines leading very shortly to stabilization of the condition with
progressive clinical deterioration.
These children were mostly from 3 to 9 months old. All patients were
studied for the presence of metabolic diseases with negative results; then
chromosomal mapping was done, also with negative results; encephalic TAC
and RMN were performed at first appearance of the symptomatology, also
with negative results.
The 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 for
all for IgM, leading us to estimate seropositivity (IgG) 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%. In all the patients we
observed diminished sideremia and a deficit of IgA and IgG with a slight
increase of GOT and GPT. None of the patients had maternally transmitted
viral encephalopathy, and in all the patients the vegetative and
relational life was quite normal 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 of CNS pathology, and these antigens indicate a possible
autoimmune immunogenetic basis for the demyelination process.
(See A.
Svejgard, P. Platz, and L. P. Ryder in Immunology Rev. 70, 1983, 193).
The
chi-square statistical analysis, with the Italian population as a control
(see 11th International Histocompatibility Workship and Conference, 1992)
demonstrated an increase in the HLA-A3 antigen (43.3% vs. 25%, P = 0.04,
after statistical correction) and 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 22/30 (73.3%) of the patients.
Additional cases are under study to better define the possible association
of HLA A3 and/or HLA DR7 with appearance of this pathology in the CNS
following vaccination. 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 the thousand different possible
haplotypes, also the problems: of molecular resemblance (see G. Laurentaci
and B. Favoino, "Immunogenetica e malattie HLA Associate," Dedalo
Litostampo, Bari, 1991), 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.
Conclusion
All the patients observed presented various physical problems. The various
types of CNS pathology could be due to a delatentization of preexisting
autoimme 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 indicate 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 thedose administered,
could demonstrate the possibility of changes in the aminoacids 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.
By
Harris L. Coulter Ph.D.
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