Environmental factors--what role in autoimmune diseases?

http://www.aarda.org/infocus_article.php?ID=33

From InFocus Newsletter, September 2006 

•  Fundamentally, all autoimmune diseases are a consequence of impaired immune function that results from interactions of genetic and environmental factors. Despite important progress, much remains to be learned about these factors and their interactions. Advances in this area are providing a foundation for more effective therapies and prevention strategies.

• Approximately one-third of the risk of developing an autoimmune disease can be attributed to heritable factors; the remainder is thought to be associated with non-inherited events.
• Some of these events arise from the randomness that characterizes human exposures; and others, from the diversity of the immune system itself--a diversity that enables the immune system to recognize a broad range of bacteria and viruses.

• These environmental factors account for the occurrence of autoimmune disease in only one member of a pair of genetically identical animals or identical twins.

• Certain environmental agents play a clear role in instigating autoimmune processes. For example, drugs such as procainamide and hydrolyzine can induce a lupus-like syndrome in genetically-susceptible individuals that remits when the drug is discontinued. Other drug-induced autoimmune diseases have been described, including some of the hemolytic anemias, thrombocytopenias, and the leukopenias.
   
• The possible role of exposure to various metals in autoimmune disease has been explored, primarily through laboratory and animal studies.

• Generally, metals inhibit immune cell proliferation and activation, with notable exceptions. Mercury, gold, and silver, for example, can induce lymphocyte proliferation and subsequent autoimmunity.

• Genetically-susceptible mice develop a lupus-like condition when dosed with mercury, silver, or gold. It is likely, however, that the autoimmune disorders that result from exposure to various metals occur through distinct mechanisms.
   
• Abnormal immune responses may also be due to a deficiency of a specific substance. For example, selenium deficiency has been linked with autoimmune thyroiditis and cardiomyopathy in humans; some people with these disorders improve when given selenium supplements. As with studies of the role of metals, the mechanism of action remains unclear. 

• Other environmental exposures have been studied, but associating such exposures with specific disorders is difficult.
• Some epidemiologic information suggests an association between dietary iodine and iodine-thyroiditis, and between silica and both scleroderma and lupus in certain industrial settings.
• Additional research has explored possible relationships between autoimmune disease and exposures to organic compounds, principally the halogenated hydrocarbon trichloroethylene (TCE) and polychlorinated biphenyls (PCBs). TCE metabolites have been associated with systemic lupus erythematosus, systemic sclerosis, and other autoimmune disorders. The evidence for PCB effects is sparse.
• Similarly, a few epidemiologic studies have examined occupational exposures to dioxins; however, firm epidemiologic evidence of a cause and effect association has yet to be shown. Similarly, investigations of exposure to pesticides and estrogenic compounds are areas of considerable research interest, but they require additional exploration.
   
• Ultraviolet radiation from sun exposure can exacerbate disease in patients with systemic lupus erythematosus.
• Other epidemiologic studies suggest that ultraviolet exposure may be protective in multiple sclerosis and rheumatoid arthritis; however, conflicting animal studies indicate that ultraviolet exposure may increase autoimmune disease risk in genetically-predisposed individuals.
   
• Infectious agents are the most often cited environmental factors implicated as triggers of autoimmune diseases. A classic example is the central role of the Group A beta-hemolytic streptococcus in the development of rheumatic heart disease. Acute Guillain-Barr? syndrome has been associated with a number of bacterial and viral infections, and reactive arthritis has been linked to a variety of intestinal infections.

• Indirect evidence has implicated a number of infections in type 1 diabetes and multiple sclerosis, and it has focused renewed attention on the possible role of Epstein-Barr virus (EBV) in lupus and rheumatoid arthritis.
   
• Despite these leads, the exact mechanisms by which infection induces a particular autoimmune disease are unknown. In the case of streptococcus, it is believed than an antigen of the microorganism resembles an antigen present in the heart and that a cross-reactive immune response to the infecting microorganism causes immune-mediated damage to the heart. The phenomenon is referred to as molecular mimicry. In other instances, microorganisms or local inflammation may alter antigens of the host so that the immune system sees them as foreign. Infections may also increase immune cell expression of co-stimulatory molecules and thus promote autoimmune responses.
  
  --Source: Progress in Autoimmune Diseases Research, NIH Autoimmune Diseases Coordinating Committee "Report to Congress," March 2005