Environmental factors, toxicants and systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an immune-complex-mediated multi-systemic autoimmune condition of multifactorial etiology, which mainly affects young women. It is currently believed that the onset of SLE and lupus flares are triggered by various environmental factors in genetically susceptible individuals. Various environmental agents and toxicants, such as cigarette smoke, alcohol, occupationally- and non-occupationally-related chemicals, ultraviolet light, infections, sex hormones and certain medications and vaccines, have been implicated to induce SLE onset or flares in a number case series, case-control and population-based cohort studies and very few randomized controlled trials. Here, we will describe some of these recognized environmental lupus triggering and perpetuating factors and explain how these factors potentially bias the immune system towards autoimmunity through their interactions with genetic and epigenetic alterations. Further in-depth exploration of how potentially important environmental factors mechanistically interact with the immune system and the genome, which trigger the onset of SLE and lupus flares, will certainly be one of the plausible steps to prevent the onset and to decelerate the progress of the disease.

Figure 1

Schematic presentation of the proposed pathways linking environmental factors to the development of systemic lupus erythematosus (SLE). See the text for details. * Denoted outside the cell in this diagram for the sake of the clarity of presentation. These processes indeed take place inside the CD4⁺ T-cell; Hg, mercury; UV, ultraviolent; PKCδ T⁵⁰⁵, phosphorylated protein kinase C δ; ERK, extracellular signal-regulated kinase; Dnmt1, DNA methyltransferase 1; IFN γ, interferon γ; and SLE, systemic lupus erythematosus.