Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis

<div><h3>Background</h3><p>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.</p> <h3>Methods and Findings</h3><p>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).</p> <h3>Conclusion</h3><p>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.</p> </div

Effects of the exposition to organic solvents on experimental models.

<p>In parenthesis is shown the model where the effect was studied. OS: Organic solvent; TCE: Trichloroethylene; DCAC: dichloroacetyl chloride; TCAH: Trichloroacetaldehyde hydrate; HgCl2: Mercuric Chloride; DCVC: dichlorovinyl-l-cysteine; PCE: Perchloroethylene; ROS: Reactive Oxygen Species; NO: Nitric Oxide; ANA: Anti-Nuclear Antibodies; TNF-α: Tumor Necrosis Factor alpha; IFN-γ: Interferon Gama; IL-4: Interleukin 4.</p

Potential molecular mechanisms implicated in solvent autoimmune disease development.

<p>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.</p

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

<p>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>I</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.</p

Characteristics of the studies examined in the meta-analysis.

<p>AD: autoimmune disease, qBHs: Quantitative score of the Bradford Hills Criteria for causation. AS: ankylosing spondylitis. RA: rheumatoid arthritis. SSc: systemic sclerosis. SLE: systemic lupus erythematous, OS: Organic solvent. GN: glomerulonephritis,NPR: National population Register; N: number of subjects in each group. OR 95% CI: Odds ratio with 95% confident interval. MS: multiple sclerosis. NA: not available data. PBC: primary biliary cirrhosis. AOR: Adjusted odds ratio. PSV: primary systemic vasculitis, WG: Wegener's granoulomatosis. RD: Raynaud's disease. TCE: trichloroethylene.</p

Systematic Review Results.

<p>Footnote: OSs: organic solvents; AD: autoimmune disease; OR: odds ratio.</p

Prevalence of Celiac Disease in Latin America: A Systematic Review and Meta-Regression

<div><p>Background</p><p>Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in susceptible individuals, and its prevalence varies depending on the studied population. Given that information on CD in Latin America is scarce, we aimed to investigate the prevalence of CD in this region of the world through a systematic review and meta-analysis.</p><p>Methods and Findings</p><p>This was a two-phase study. First, a cross-sectional analysis from 981 individuals of the Colombian population was made. Second, a systematic review and meta-regression analysis were performed following the Preferred Reporting Items for Systematic Meta- Analyses (PRISMA) guidelines. Our results disclosed a lack of celiac autoimmunity in the studied Colombian population (i.e., anti-tissue transglutaminase (tTG) and IgA anti-endomysium (EMA)). In the systematic review, 72 studies were considered. The estimated prevalence of CD in Latin Americans ranged between 0.46% and 0.64%. The prevalence of CD in first-degree relatives of CD probands was 5.5%. The coexistence of CD and type 1 diabetes mellitus varied from 4.6% to 8.7%, depending on the diagnosis methods (i.e., autoantibodies and/or biopsies).</p><p>Conclusions</p><p>Although CD seems to be a rare condition in Colombians; the general prevalence of the disease in Latin Americans seemingly corresponds to a similar scenario observed in Europeans.</p></div

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

<p>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.</p

Presence of HLA in celiac disease patients.

<p>* Caucasian origin.</p><p>Presence of HLA in celiac disease patients.</p

Flow chart of the systemic literature review.

<p>VHL: virtual health library. CD: Celiac disease. LA: Latin America.</p