Review
Occupational exposures and autoimmune diseases

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Abstract

Autoimmune diseases are pathologic conditions defined by abnormal autoimmune responses and characterized by immune system reactivity in the form of autoantibodies and T cell responses to self-structures. Here we review the limited but growing epidemiologic and experimental literature pertaining to the association between autoimmune diseases and occupational exposure to silica, solvents, pesticides, and ultraviolet radiation. The strongest associations (i.e., relative risks of 3.0 and higher) have been documented in investigations of silica dust and rheumatoid arthritis, lupus, scleroderma and glomerulonephritis. Weaker associations are seen, however, for solvent exposures (in scleroderma, undifferentiated connective tissue disease, and multiple sclerosis) and for farming or pesticide exposures (in rheumatoid arthritis). Experimental studies suggest two different effects of these exposures: an enhanced proinflammatory (TH1) response (e.g., TNF-α and IL-1 cytokine production with T cell activation), and increased apoptosis of lymphocytes leading to exposure to or modification of endogenous proteins and subsequent autoantibody formation. The former is a general mechanism that may be relevant across a spectrum of autoimmune diseases, whereas the latter may be a mechanism more specific to particular diseases (e.g., ultraviolet radiation, Ro autoantibodies, and lupus). Occupational exposures are important risk factors for some autoimmune diseases, but improved exposure assessment methods and better coordination between experimental/animal models and epidemiologic studies are needed to define these risks more precisely.

Introduction

Autoimmunity, the development of immune system reactivity in the form of autoantibodies and T cell responses to self-structures, has held a special fascination for researchers since its theoretical description in 1901 [1]. Autoimmunity, rather than being counterproductive to survival, may be a normal and perhaps necessary part of immune regulatory networks that sustain health [2], [3]. It is not known why autoimmunity sometimes progresses to pathologic states (autoimmune diseases) characterized by tissue destruction, mediated by humoral and/or cellular self-reactive processes. The dozens of known autoimmune diseases range from tissue-specific (e.g., multiple sclerosis, type I diabetes) to systemic disorders (e.g., scleroderma, rheumatoid arthritis) and from childhood to adult onset conditions [4] (Table 1). At least 3% of the United States population is affected by an autoimmune disease [5] and autoimmune diseases are among the leading causes of death for women under the age of 65 [6]. Autoimmune diseases may involve nearly any organ or tissue of the body. Most autoimmune diseases disproportionately affect women, and in some conditions (thyroiditis, scleroderma, systemic lupus erythematosus) more than 85% of patients are female.

Patterns of disease occurrence in families, disease concordance rates in twins, disease associations with specific candidate genes, and animal models strongly suggest a role of genetic factors in the etiology of autoimmune disease [7], [8]. The genes most commonly associated with autoimmune disease are those that regulate immune responses such as the major histocompatability complex (MHC) genes and genes affecting cytokine production. However, human autoimmune diseases do not follow the classic modes of Mendelian transmission. There may be a number of shared or common “autoimmunity genes” that increase risk for the development of many autoimmune disorders [9], while other genes and environmental influences may determine the particular autoimmune illness that develops in an individual [10]. There is strong support for the concept that autoimmune diseases are multifactorial disorders that result from the interactions of genes and environmental factors [11].

In this paper, we review the epidemiologic and experimental literature pertaining to occupational exposures and autoimmune disease. We have focused on agents that represent a spectrum, in terms of the extent of epidemiologic and experimental studies, the specific diseases involved, and the role of the agents in induction versus exacerbation of disease. The agents discussed include silica dust (quartz), solvents, pesticides, and ultraviolet radiation.

Section snippets

Silica

Crystalline silica or silicon dioxide (SiO2), the most abundant mineral in the earth's crust, is found in rock, sand, and soil. The traditional “dusty trades” include work in mines, quarries, foundries, roadway and other construction sites, masonry, sandblasting, and the production of pottery, glass, and tile [12]. Extensive exposure to crystalline silica can cause silicosis, a progressive and ultimately fatal form of fibrotic lung disease [13].

The association between occupational exposure to

Conclusions

It is clear that occupational exposures can influence the development and course of autoimmune disease. Experimental studies suggest that there may be common mechanisms among seemingly diverse exposures. These mechanisms may be relevant across the spectrum of autoimmune diseases. Agents may act as adjuvants, enhancing the immune response, modify endogenous proteins leading to self-reactivity, or induce apoptosis resulting in exposure of sequestered antigens. Immunomodulatory agents may have

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