Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis

Abstract

Background: Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs.

Methods and findings: The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25-1.92; p-value<0.001).

Conclusion: Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.

Figure 1. Systematic Review Results.

Footnote: OSs: organic solvents; AD: autoimmune disease; OR: odds ratio.

Figure 2. Forest plot of studies meta-analyzed: association between organic solvents and autoimmune disease as a trait.

Footnote: final common effect size based on a random model. Odds Ratio (95%CI) with raw data from case control and cohort designed studies were included. The most relevant outcome per author was included. The relative weight of each study is included. GN: glomerulonephritis; MS: multiple sclerosis; PBC: primary biliary cirrhosis; PSV: primary systemic vasculitis; RA: rheumatoid arthritis; RP: Raynaud disease; SLE: systemic lupus erythematosus; SSc: systemic sclerosis. Diot, et al 1: organic solvent as a whole; Thompson AE, et al 1: turpentine exposure (the most significant result); Nelson NA, et al 1. 1994: disabled population; Purdie GL, et al 1. 2011 confirmed RP population.

Figure 3. Forest plot of studies meta-analyzed grouping by comparison of specific autoimmune diseases.

Footnote: random effect model showing significant association between SSC and OSs exposure. PBC and PSV included only one study (100% of the weight). Q value for SSc analysis: 33.7, I ²:79,2, Degree of freedom (Q):7, p-value<0,0001. GN: glomerulonephritis; MS: multiple sclerosis; PBC: primary biliary cirrhosis; PSV: primary systemic vasculitis; RA: rheumatoid arthritis; RP: raynaud disease; SLE: systemic lupus erythematosus; SSc: systemic sclerosis. Diot, et al 1: organic solvent as a whole; Thompson AE, et al 1: turpentine exposure (the most significant result); Purdie GL, et al 1: confirmed RP population; Nelson NA, et al 1. 1994: disabled population.

Figure 4. Potential molecular mechanisms implicated in solvent autoimmune disease development.

Footnote: Solid red arrows represent known paths. Yellow dashed arrow represents hypothetical mechanisms (warranting future research), and red dashed line represents an inhibited process. In susceptible individuals, activation paths are stronger (black arrows). See text for details. ROS: Reactive oxygen Species; NO: Nitric Oxide.