components of the immune system, or they could cause a combination of these effects. Studies suggest that the duration and number of exposures to the same or different agents, as well as the dosage and route of administration of the agent, affect the risks of developing specific autoimmune disorders (Miller, 1997).
Research suggests that the same autoimmune syndrome can be induced by different environmental agents, even though each agent is associated with different HLA risk factors. In contrast, a similar syndrome induced by different agents can sometimes be associated with the same genetic risk factor (Love and Miller, 1993). A lupus-like syndrome can be caused by the heart medication procainamide in association with the HLA subtype DR6, for example, or by the high blood pressure drug hydralazine in association with the HLA subtype DR4. In contrast, two scleroderma-like syndromes, one due to contaminated rapeseed oil and another associated with ingestion of certain manufacturing batches of L-tryptophan, are both associated with the HLA subtype DR4 (Miller, 1997).
Genetic factors that also might influence the risk of developing autoimmune disorders and other possible adverse reactions from vaccines are human endogenous retroviruses (HERVs). HERVs are genetic sequences that resemble retroviruses and that may either be a precursor or a product of viruses whose genes have become inserted into all human DNA. HERVs usually cannot actively infect cells, like viruses can, but evidence suggests that their genes can be expressed, possibly to the point of generating proteins, in certain tissues under certain circumstances. Factors proposed to possibly influence HERV expression include hormones, X rays, compounds generated by the immune system in response to infection, viruses, and steroids (Urnovitz and Murphy, 1996).
A mouse model also suggests that certain genes can influence the expression of specific endogenous retroviruses (ERVs). In this mouse model, mice that have a gene that fosters expression of ERVs develop an age-dependent paralyzing disorder when they are infected with a virus that, without ERV expression, is normally harmless (Murphy et al., 1983).
The possibility that ERVs can be part of the disease process, as in the previously mentioned mouse model, has prompted one workshop speaker to consider the possibility that HERVs play a role in certain human diseases or in adverse events following vaccination. Because HERVs have the enzyme needed to copy and incorporate viral genetic material into human DNA, HERVs theoretically might copy and incorporate the viral genetic material presented in vaccines or natural infections (Urnovitz et al., 1996). Urnovitz hypothesized that these fragments normally would not be expressed but that an infection by another organism, certain hormones, or injury might activate them.