Dr. Ron’s Research Review – October 3, 2012

This week’s research review focuses on vaccinations and autoimmune disease.

Wraith reviews the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings. (Wraith, Goldman et al. 2003)

Guillain-Barre syndrome is a classical autoimmune disease triggered by infection or vaccination. (Israeli, Agmon-Levin et al. 2012)

People with autoimmune disorders are pre-disposed, such as in an "autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease". (Perdan-Pirkmajer, Thallinger et al. 2012)

Koenig develops a classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). Hypersensitivity reactions and molecular mimicry vaccine-related reactions are incorporated into this mechanistic scheme. (Koenig, Sutherland et al. 2011)

Dr. Ron


Articles

Guillain-Barre syndrome--a classical autoimmune disease triggered by infection or vaccination

            (Israeli, Agmon-Levin et al. 2012) Download

Guillain-Barre syndrome (GBS) is a rare autoimmune disorder, the incidence of which is estimated to be 0.6-4/100,000 person/year worldwide. Often, GBS occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal microbial infection. The disorder is sub-acute developing over the course of hours or days up to 3 to 4 weeks. About a third of all cases of Guillain-Barre syndrome are preceded by Campylobacter jejuni infection. C. jejuni strains isolated from GBS patients have a lipooligosaccharide (LOS) with a GM1-like structure. Molecular mimicry between LOS and the peripheral nerves as a cause of GBS was demonstrated in animal models of human GBS. Following the "swine flu" virus vaccine program in the USA in 1976, an increase in incidence of GBS was observed and the calculated relative risk was 6.2. Later studies have found that influenza vaccines contained structures that can induce anti-GM1 (ganglioside) antibodies after inoculation into mice. More recent information has suggested that the occurrence of GBS after currently used influenza and other vaccines is rare. GBS involves genetic and environmental factors, may be triggered by infections or vaccinations, and predisposition can be predicted by analyzing some of these factors.

Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination

            (Koenig, Sutherland et al. 2011) Download

In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post-licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination.


Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease

            (Perdan-Pirkmajer, Thallinger et al. 2012) Download

Vaccines have undoubtedly brought overwhelming benefits to mankind and are considered safe and effective. Nevertheless, they can occasionally stimulate autoantibody production or even a recently defined syndrome known as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is scarce data regarding autoimmune response after seasonal/influenza A (H1N1) vaccine in patients with autoimmune inflammatory rheumatic disease (AIRD). The objective of our study was therefore to determine autoimmune response in a large group of AIRD patients vaccinated against seasonal and/or H1N1 influenza. We conducted a prospective cohort study with a 6-month follow-up. Two-hundred and eighteen patients with AIRD (50 vaccinated against seasonal influenza, six against H1N1, 104 against both, 58 non-vaccinated controls) and 41 apparently healthy controls (nine vaccinated against seasonal influenza, three against H1N1, 18 against both, 11 non-vaccinated controls) were included. Blood samples were taken and screened for autoantibodies [antinuclear antibody (ANA), anti-extractable nuclear antigen (anti-ENA), anticardiolipin (aCL) IgG/IgM antibodies, anti-beta 2-glycoprotein I (anti-beta2GPI)] at inclusion in the study, before each vaccination, 1 month after the last vaccination and 6 months after inclusion. For non-vaccinated participants (patients and healthy controls) blood samples were taken at the time of inclusion in the study and 6 months later. We report that after the administration of seasonal/H1N1 vaccine there were mostly transient changes in autoantibody production in AIRD patients and in healthy participants. However, a small subset of patients, especially ANA-positive patients, had a tendency towards anti-ENA development. Although no convincing differences between the seasonal and H1N1 vaccines were observed, our results imply that there might be a slight tendency of the H1N1 vaccine towards aCL induction. Although seasonal and H1N1 vaccines are safe and effective, they also have the potential to induce autoantibodies in selected AIRD patients and healthy adults. Follow-up of such individuals is proposed and further research is needed.


Vaccination and autoimmune disease: what is the evidence?

            (Wraith, Goldman et al. 2003) Download

As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings.

References

Israeli, E., N. Agmon-Levin, et al. (2012). "Guillain-Barre syndrome--a classical autoimmune disease triggered by infection or vaccination." Clin Rev Allergy Immunol 42(2): 121-30.

Koenig, H. C., A. Sutherland, et al. (2011). "Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination." Vaccine 29(5): 913-9.

Perdan-Pirkmajer, K., G. G. Thallinger, et al. (2012). "Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease." Lupus 21(2): 175-83.

Wraith, D. C., M. Goldman, et al. (2003). "Vaccination and autoimmune disease: what is the evidence?" Lancet 362(9396): 1659-66.