Environmental Influences on Systemic Lupus Erythematosus Expression

Kamen, Diane L.

doi:10.1016/j.rdc.2014.05.003

Cited by 109 publications

(65 citation statements)

References 62 publications

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“…[1][2][3] The disorder can involve many organ systems of the body, and manifests clinically in a relapsing and remitting manner. [1][2][3] SLE is characterized by the production of autoantibodies directed against nuclear and cytoplasmic antigens, and although its etiology is not wellunderstood, numerous genetic, epigenetic, and environmental risk factors have been identified.…”

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confidence: 99%

“…[1][2][3] SLE is characterized by the production of autoantibodies directed against nuclear and cytoplasmic antigens, and although its etiology is not wellunderstood, numerous genetic, epigenetic, and environmental risk factors have been identified. [1][2][3] Clinical management is based on disease severity, and includes the use of anti-inflammatory drugs (steroidal and nonsteroidal), immunosuppressive drugs, and biologic agents.…”

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confidence: 99%

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A Systematic Review and Meta-analysis of Prevalence of Biopsy-Proven Lupus Nephritis

et al. 2018

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Objectives: This study aims to conduct a meta-analysis to clarify the epidemiologic characteristics of biopsy-proven lupus nephritis (BPLN), including those relating to its prevalence and prognosis. Patients and methods: A literature search for relevant studies was conducted in the electronic databases of PubMed, Google Scholar, Embase, and Cochrane trial register. The following search terms were used for original articles published between January 1982 and April 2016: "lupus nephritis" or systemic lupus erythematosus ('SLE') or 'systemic lupus erythematous' and "pathology" or 'epidemiology' or prevalence or incidence. Pooled estimates with 95% confidence intervals were calculated. Results: Nineteen studies were included (mean age of SLE patients at renal biopsy: ~30 years). Of total BPLN patients, 85% were females. BPLN developed in 29% of SLE patients, and accounted for 60% of secondary glomerular diseases in renal biopsy databases. BPLN prevalence among SLE patients was higher in Saudi Arabia compared with pooled Europe/USA data (43% vs 26%, p<0.05). Pooled BPLN prevalence among secondary glomerular diseases patients was higher in Asian/Latin American countries than in Europe (63% vs 34%, p<0.05). Overall five-, 10-and 20-year survival rates of BPLN patients were 94%, 86%, and 71%, respectively, which were higher than those before 1995 (84%, 72%, and 52%, respectively) and lower than those after 1995 (96%, 89%, and 80%, respectively) (all p<0.05). Class IV nephritis, present in 40% of BPLN patients, was a risk factor for renal failure that contributed to poor prognosis. Conclusion: Lupus nephritis is a common complication of young female patients with SLE, and the most prevalent etiology of secondary glomerular diseases. Attention should be paid to class IV nephritis due to its high frequency and association with poor prognosis.

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confidence: 99%

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confidence: 99%

A Systematic Review and Meta-analysis of Prevalence of Biopsy-Proven Lupus Nephritis

et al. 2018

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“…For instance, the SLE KEGG pathway was one of the most altered. This in all likelihood is not coincidental as the exposure to PCBs has been linked to an increased incidence of SLE (Kamen 2014). Histone gene expression was the most disturbed of the SLE pathways in our study (Supplementary Material 3).…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126

et al. 2018

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Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2235-7) contains supplementary material, which is available to authorized users.

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“…It has been suggested that moderate alcohol consumption may be protective , but these results may also be due to other confounding factors related to lifestyle and socio‐economic status. Amongst occupational risk factors, exposure to silica is considered an established SLE risk factor with several studies showing similar results. It should, however, be noted that silica exposure results from typically male occupations such as mining.…”

Section: Environmental Factorsmentioning

confidence: 92%

“…It has been suggested that moderate alcohol consumption may be protective [60,68], but these results may also be due to other confounding factors related to lifestyle and socio-economic status. Amongst occupational risk factors, exposure to silica is considered an established SLE risk factor [69] with Treatment TNF blockers and other biological therapies have been used in the treatment of rheumatoid arthritis and spondylarthropathies for many years, and this has dramatically changed the rheumatological landscape. Meanwhile, all Phase III placebo-controlled RCTs of different biological therapies in SLE were unsuccessful until studies in which treatment with belimumab showed significant effects on a new responder index: the SLE Responder Index (SRI).…”

Section: Environmental Factorsmentioning

confidence: 99%