Role of Immunogentics in the diag. of postvaccinal CNS pathology

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an oldie that was past around recently -

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Role of Immunogenetics in the Diagnosis of Postvaccinal CNS Pathology

Massimo Montinari*, Biagio Favoino**, and o***

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 " Hahnemann " (LUIMO). Translated from Italian by

L. Coulter, Ph.D.

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. taci 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.