ASIA: A New Way to Put the Puzzle Together

A causal link between vaccines and autoimmunity was noted in 1976 during an outbreak of Guillain-Barré syndrome (GBS) that followed immunization with the “swine flu” vaccine.²² Causal relationships have also been accepted for transverse myelitis following an oral polio vaccine, autoimmune thrombocytopenia after measles-mumps-rubella, and arthritis following diphtheria-tetanus-pertussis.³

Additionally, a series of animal studies supported such a cause-and-effect interaction. Thus, immunization of young dogs resulted in the production of autoantibodies including lupus-associated ones. In diabetes-prone animals (e.g., NOD mice and BB rats) vaccination was associated with an increased incidence of diabetes and recently intraperitoneal immunization of salmon fish with oil-adjuvanted vaccines resulted in the production of autoantibodies thrombo-embolic disease, and immune-mediated glomerlulonephritis.³

The efficacy of most currently used vaccines depends on the presence of an adjuvant in conjunction with a foreign antigen corresponding to a component of an infectious agent.^10,11 Adjuvants increase the protective and lasting immune response to the immunizing antigen and enable the decrease of the antigen amount and thereby the production of a larger amount of vaccines.¹⁰ One of the most evaluated post-vaccination autoimmune conditions is MMF, where a causal link to the vaccine adjuvant alum has been delineated.

MMF is a rare immune mediated muscles disease caused by deposition of aluminum, used to adjuvant different vaccines.⁵ MMF is characterized by a local active lesion at the site of inoculation as well as systemic signs and symptoms that resemble the ones described in relation to silicone exposure.⁵ These include myalgias, arthralgias, marked asthenia, muscle weakness, chronic fatigue, fever, and in some cases the appearance of a demyelinating disorder. Elevated creatine kinase and erythrocyte sedimentation rate as well as the appearance of autoantibodies, and myopathic electromyography changes also have been documented.⁵

The local lesion of MMF results from persistence of aluminum adjuvant at the site of inoculation for months and even 8–10 years following immunization.⁵ Intriguingly, the discrepancy between the wide application of aluminum hydroxide and the rarity of MMF recently has been resolved by the observations that MMF appears mainly in genetically susceptible subjects carrying the HLA–DRB1*01. This connection was first described in identical twin sisters diagnosed with MMF and later on in six of nine MMF patients, compared with 17% of 230 controls (O.R. of 9.8; 95% confidence interval 2.0–62.2).²³

Another syndrome characterized by fatigue, neurological deficits, cognitive dysfunctions, and motor neuron disease is GWS. This syndrome may result from an adjuvant effect following multiple vaccinations performed over a short period of time. During the Gulf War, the veterans’ vaccination protocol included the anthrax vaccine, administered in a six-shot regimen and adjuvanted by aluminium hydroxide and squalene.10 In a relatively large study of 144 Gulf War-era veterans, 95% of overtly ill deployed GWS patients had antibodies to squalene. Furthermore, 100% of GWS patients immunized for service who did not deploy but had the same manifestations as those who did deploy had antibodies to squalene. In contrast, none of the control groups that incorporated patients with autoimmune diseases, healthy controls, and Persian Gulf veterans not showing signs of GWS had antibodies to squalene. Thus, although the pathogenesis of GWS is under scrutiny, the data assembled at this time highlight the possible role of adjuvants in this syndrome.

ASIA