Understanding the role of environmental factors in the development of systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a multisystem disease with a complex etiology. Its risk is higher among women, racial and ethnic minorities, and individuals with a family history of SLE or related autoimmune diseases. It is believed that genetic factors interact with environmental exposures throughout the lifespan to influence susceptibility to developing SLE. The strongest epidemiologic evidence exists for increased risk of SLE associated with exposure to crystalline silica, current cigarette smoking, use of oral contraceptives, and postmenopausal hormone replacement therapy, while there is an inverse association with alcohol use. Emerging research results suggest possible associations of SLE risk with exposure to solvents, residential and agricultural pesticides, heavy metals, and air pollution. Ultraviolet light, certain infections, and vaccinations have also been hypothesized to be related to SLE risk. Mechanisms linking environmental exposures and SLE include epigenetic modifications resulting from exposures, increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal effects. Research needs to include new studies of environmental risk factors for SLE in general, with a focus on lifetime exposure assessment. In addition, studies in susceptible subgroups, such as family members, studies based on genetic risk profiles, and studies in individuals with evidence of pre-clinical autoimmunity based on the detection of specific auto-antibodies are also required. Understanding the role of environmental exposures in the development of SLE may help identify modifiable risk factors and potential etiological mechanisms.

Keywords: Environment; Exposure; Pathogenesis; Risk factor; SLE; Systemic lupus erythematosus.

Figure 1

Environmental Influences on SLE across the lifecourse.^{1 1}Against a background of genetic susceptibility, sex (female), and developmental stage, multiple environmental exposures and stochastic factors contribute together and over time to epigenetic changes and immune dysregulation through a variety of mechanisms, resulting in functional changes, loss of tolerance and autoimmunity, plus inflammation, and leading to the development of SLE.