Epidemiology of environmental exposures and human autoimmune diseases: Findings from a National Institute of Environmental Health Sciences Expert Panel Workshop

Abstract

Autoimmune diseases (AID) are a collection of many complex disorders of unknown etiology resulting in immune responses to self-antigens and are thought to result from interactions between genetic and environmental factors. Here we review the epidemiologic evidence for the role of environmental factors in the development of human AID, the conclusions that can be drawn from the existing data, critical knowledge gaps, and research needed to fill these gaps and to resolve uncertainties. We specifically summarize the state of knowledge and our levels of confidence in the role of specific agents in the development of autoimmune diseases, and we define the areas of greatest impact for future investigations. Among our consensus findings we are confident that: 1) crystalline silica exposure can contribute to the development of several AID; 2) solvent exposure can contribute to the development of systemic sclerosis; 3) smoking can contribute to the development of seropositive rheumatoid arthritis; and 4) an inverse association exists between ultraviolet radiation exposure and the risk of development of multiple sclerosis. We suggest that more studies of phenotypes, genotypes, and multiple exposures are needed. Additional knowledge gaps needing investigation include: defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and elucidating mechanisms for disease development. Addressing these essential issues will require more resources to support research, particularly of rare AID, but knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of AID in the future.

Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells

“…Understanding the unfavorable interactions between genes and environment are critical in understanding the pathophysiology of autoimmune diseases (18,19). Insufficient vitamin D intake, increased body mass index, and smoking are environmental risk factors for a number of autoimmune diseases.…”

Increasing prevalence of Addison's disease in German females: health insurance data 2008–2012

“…Other environmental agents, such as viral infections, cigaret smoking, and pollutants, as well as a reduced microbial burden during early life, have been found to influence the development of autoimmune diseases, presumably by epigenetic changes (26,27,28).…”

Differential Features of AIRE-Induced and AIRE-Independent Promiscuous Gene Expression in Thymic Epithelial Cells

“…Failure to establish or maintain self-tolerance causes autoimmunity, which has a major impact on human health. Classic autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis affect ∼4% of the general population (6). Induction of so-called "central tolerance" in the thymic medulla depends on ectopic expression of proteins otherwise restricted to differentiated organs in the periphery (7).…”