Environment, autoantibodies, and autoimmunity.

Abstract

Susceptibility to autoimmune disease is multifactorial and includes genetic predisposition, gender, ethnicity, age, and environment. While no single factor has been identified as preeminent, the role of the environment has garnered increasing interest. This reflects the ubiquitous nature of the environment, which encompasses everything around us including the air we breathe, the water we drink, the food we eat, synthetic and natural chemicals, microorganisms, industrial by-products, and physical factors such as radiation (1). The most convincing evidence for a role of exogenous factors in autoimmunity comes from studies implicating numerous medications in the induction of autoimmune disease, particularly the association of drug-induced systemic lupus erythematosus (SLE) with procainamide and hydralazine (2). Identification of the causal role of medications in the induction of autoimmune disease is due in large part to the fact that medications are taken under medical supervision where drug exposure and possible side effects can be closely monitored. This is not the case with non-therapeutic exposure to environmental factors where contact may include numerous exogenous factors at any particular time. Nonetheless, evidence for the association of (non-therapeutic) environmental exposure with autoimmunity has come from two well documented exposures. In 1981, in Spain, the ingestion of analine adulterated rapeseed oil was linked to a previously unknown disease, subsequently called toxic oil syndrome (TOS), which was characterized by myalgias, peripheral eosinophilia, and pulmonary infiltrates (3). The adulterated oil was sold as “olive oil” by street vendors and subsequently used for cooking. The determination that the adulterated oil was the cause of TOS was based on robust epidemiological evidence. More than 20,000 people were affected and some 2,000 perished. Chronic conditions, including scleroderma and neurologic changes, have been described in the survivors. A clinically similar, though epidemiologically distinct, syndrome was identified in United States in 1989 (3, 4). Eosinophilia myalgia syndrome (EMS) affecting approximately 1,500 individuals was suggested to be due to ingestion of certain lots of l-tryptophan from a single manufacturer. Akin to TOS, EMS is a scleroderma-like syndrome found more frequently in women but unlike TOS was not restricted to a geographical area. The acute phase of the syndrome was characterized by myalgia and eosinophilia, followed by chronic cutaneous lesions, progressive neuropathy, and myopathy. These causative exposures are rare examples in a field hampered by the difficulty of linking putative environmental risk factors with autoimmune disease in humans. Recently, the National Institute of Environmental Health Sciences (NIEHS) convened an expert panel in a workshop setting to review the role of the environment in the development of autoimmune disease. The meeting addressed specific areas of mechanisms, animal models, epidemiology, diagnostic criteria, and exposure assessment focusing, in particular, on the contribution of chemical, physical, and biological agent exposures; medications were not considered. A series of papers were published summarizing the workshop findings (5–8), and a consensus statement was recently published (9). Together these publications constitute the most recent summary of the state of knowledge on the role of environmental exposures in autoimmune disease. In this opinion piece, I will expand upon some of the findings of the NIEHS workshop and our own studies to examine how environmental exposure can contribute to our understanding of autoimmunity and autoimmune diseases.