ReviewVaccination and autoimmune disease: what is the evidence?
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Autoimmune disease and infection
Human beings have a highly complex immune system that evolved from the fairly simple system found in invertebrates. The so-called innate invertebrate immune system responds non-specifically to infection, does not involve lymphocytes, and hence does not display memory. The adaptive immune system, shared by vertebrates, displays both specificity and memory, and is designed to provide protection against almost all infections. Furthermore, polymorphisms in genes that control the immune system
Molecular mimicry
A popular explanation for how infectious agents stimulate autoimmunity in an antigen-specific way is via molecular mimicry.9 Antigenic determinants of microorganisms can thus be recognised by the host immune system as being similar to antigenic determinants of the host itself (figure 1). Molecular mimicry among sugar structures is common and leads to numerous manifestations of infection-associated and antibody-mediated neuropathies.10, 11 For example, about a third of all cases of
Vaccination and autoimmune disease
The medical literature is full of claims and counter claims with respect to the risk of autoimmune disease as a consequence of vaccination. Only in a few rare cases, however, has autoimmune pathology been firmly associated with particular vaccines. For example, a form of Guillain-Barre syndrome (polyradiculoneuritis) was associated with the 1976–77 vaccination campaign against swine influenza, using the A/New Jersey/8/76 swine-flu vaccine.48 The estimated attributable risk of vaccine- related
Hepatitis B and multiple sclerosis
The possibility of an association between the hepatitis B vaccination and development of multiple sclerosis was first raised in France, after a report of 35 cases of primary demyelinating events occurring at a hospital in Paris between 1991 and 1997, within 8 weeks of recombinant hepatitis B vaccine injection.57, 58 The neurological manifestations were similar to those observed in multiple sclerosis. There were inflammatory changes in the cerebrospinal fluid and lesions were noted in the
Diabetes
Over the past few decades, there has been a regular increase in the incidence of type 1 diabetes in most countries of the world. That childhood vaccines have been identified as a potential trigger event for this disease is, therefore, not surprising.
This possibility has been assessed in a few epidemiological studies. Results of a case-control study done in Sweden in the mid-1980s did not indicate any great effect of vaccination against tuberculosis, smallpox, tetanus, pertussis, or rubella on
How can a doctor assess a potential link
There exist no general criteria for diagnosing vaccine-related autoimmune disease, which has to be assessed on a case-by-case basis. Appropriate epidemiological studies should be done before a particular autoimmune clinical condition is associated with a given vaccination. Such investigation can then be followed by the identification of known biological markers of the identified autoimmune disease in other vaccinees. However, the degree of vaccine-related risk should always be compared with
Consistency and strength
The association of a purported autoimmune event with the administration of a vaccine should be consistent. Therefore, the findings should be the same if the vaccine is given to a different group of people, by different investigators not unduly influencing one another, and irrespective of the method of investigation. The association should be strong in an epidemiological sense.
Specificity
The association should be distinctive and the adverse event linked uniquely or specifically to the vaccine concerned. The association should, for instance, not arise frequently, spontaneously, or commonly in association with other external stimuli or conditions. An adverse event could be caused by a vaccine adjuvant or additive, rather than by its active component, hence spuriously affecting the specificity of the association between vaccine and adverse event.
Temporal relation
There should be a clear temporal relation between the vaccine and the adverse event, in that receipt of the vaccine should precede the earliest manifestation of the event or should occur a few weeks before a clear exacerbation of a continuing condition. Therefore, an association between vaccine administration and an autoimmune adverse event is most likely to be considered strong when the evidence is based on:
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the results of carefully undertaken clinical trials for which a study design was
New-generation vaccines
Although available epidemiological data are reassuring we must remain vigilant, particularly with respect to some of the new-generation vaccines. Special attention should be paid to new vaccine adjuvants, especially when they produce strong, innate responses.67 Additionally, cancer vaccines based on dendritic cells pulsed with tumour antigens carry a substantial risk of autoimmunity.68
During the course of vaccine development, only a comprehensive and multidisciplinary strategy can help to
Concluding remarks
A clear distinction should be made between autoimmunity and autoimmune disease. Autoimmunity is a feature of the normal healthy immune system. There is little doubt that laboratory measurable signs of autoimmunity can associate with infection and might occasionally appear after vaccination. It is comforting to appreciate that the immune system has evolved sufficient fail-safe mechanisms to ensure that these signs rarely develop into clinical disease.
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