Study Highlights Systemic Lupus Erythematosus and Environmental Risk Factors

Ines Martins, PhD avatar

by Ines Martins, PhD |

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shutterstock_121847875Systemic lupus erythematosus (SLE) is an immune multi-systemic autoimmune condition that mainly affects young women. Current evidence from population-based studies and randomized controlled trials indicated the onset of SLE and lupus flares is triggered by various environmental factors, such as cigarette smoke, alcohol, occupationally- and non-occupationally-related chemicals, ultraviolet light, infections, sex hormones and certain medications and vaccines, in genetically susceptible individuals.

Anselm Mak and Sen Hee Tay, from the Division of Rheumatology, Department of Medicine, University Medicine Cluster, Singapore and from the Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, conducted a review of evidence of these environmental risk factors and clarified how they impact the immune system, through their interactions with genetic and epigenetic alterations. Some examples are worth to be considered.

In terms of Molecular Mechanisms, studies have been specially focused on the role CD4+ in T-cells, and their reactive response to self-class MHC II molecules in SLE. Evidences from trials with animals models of SLE suggest that the presence of environmental, genetic and epigenetic factors are necessary to induce lupus. One example is the development of anti-dsDNA antibodies and an interferon (IFN) signature of leukocytes without tissue damage in transgenic C57Bl/6 mice, that express a dominant negative ERK in T-cells when they were fed with doxycycline in water. When C57Bl/6 mice were crossed with lupus-prone SJL mice, which carry lupus-susceptible genes, the resultant C57Bl/6xSJL mice developed immune-complex-mediated glomerulonephritis besides lupus serology and the IFN signature.

With regards to Ultraviolent Light, studies found that UV-A1 and UV-B, can induce disease flares in patients with SLE and trigger disease onset of SLE, however, studies have concluded that this depends on the dose of UV. Intermediate- and high-dose UV-B exposures promote pro-inflammatory apoptosis and necrosis, accompanied by the release of auto antigens and a large amount of pro-inflammatory cytokines, which trigger the inflammatory response.

Vitamin D Deficiency occurs due to minimal UV light exposure. Actually, in a recent study, a 20-ng/mL increase in serum 25-OH vitamin D was shown to be associated with a 15% decrease in the odds of clinically-important proteinuria (urine protein-to-creatinine ratio > 0.5) in patients with SLE.

Smoking habits are a known risk factor for many diseases. In the case of SLE, accumulating evidence shows for example that smoking is associated with skin flares in patients with SLE. The authors argued that it is likely that tobacco smoke may have reduced the efficacy of antimalarials, which eventually induces exacerbation of cutaneous lupus. From the studies analyzed, the authors concluded that there is no causality in terms of alcohol consumption and SLE.

In terms of occupationally- and Non-Occupationally-Related Chemicals, studies have found that people working in the rural farming industry and sandblasting may be exposed excessively to crystalline silica. Silica is an adjuvant that can induce the production of IL-1 and tumor necrosis factor α (TNF α), thus increasing the risk of SLE. Other compounds that have been found to increase the risk of SLE are polychlorinated biphenyls/dibenzofurans, mercury (Hg), liquid solvents and pesticides. Moreover, lipstick and hair dye contain compounds such as eosin, phthalates and aromatic amines that have been reported to induce onset of SLE.

In their review, the authors did not found evidence from large case-control and prospective studies of exacerbation of existing SLE and the triggering of the onset of SLE in the most commonly prescribed vaccines, including influenza, hepatitis B, human papilloma virus and varicella. From the studird’ analyses, the authors indicate that certain medications can induce lupus-like disease. These include, for example, procainamide, Hydralazine, estrogens.

Based on the current evidence, the researchers indicate that the studies published to date regarding the environmental factors related with the occurrence of SLE are mainly case-control studies that cannot establish a causative effect. Thus, the authors indicate the need of large and multi-center prospective studies are required to address the cause-effect relationship. In terms of meta-analysis, the authors note that heterogeneity in population, data collection, definition of disease and statistical methods can weaken the validity of the effect size. In their review, they recommend further studies based on the molecular mechanisms and pathways involved in the abilities of various environment agents of interest to induce SLE.

The review entitled “Environmental Factors, Toxicants and Systemic Lupus Erythematosus”, was recently published in The International Journal of Molecular Sciences.