Abstract
Farming and pesticide use have been associated with systemic autoimmune diseases, and while certain organochlorine insecticides and other pesticides are suspected to influence risk, the role of specific pesticides in the development of systemic autoimmunity is not known. We measured serum antinuclear autoantibodies (ANA) by immunofluorescence on Hep-2 cells in 668 male farmers in the study of Biomarkers of Exposure and Effect in Agriculture (BEEA; 2010–2013), an Agricultural Health Study (AHS) subcohort. We examined ANA in relation to lifetime use of 46 pesticides first reported at AHS enrollment (1993–1997) and updated at intervals through BEEA enrollment. Odds ratios (OR) and 95% confidence intervals (CI) were estimated after adjusting for age, state, education, season of blood draw, current pesticide use, and correlated pesticides. Having ANA antibodies (3 or 4+ intensity at a 1:80 dilution, 21% of study participants) was associated with a reported history of seeking medical care due to exposure to pesticides (OR 2.15; 95%CI 1.17, 3.95), use of the fumigant methyl bromide (OR 3.16; 95%CI 1.05, 9.5), and use of petroleum oil/distillates (OR 1.50; 95%CI 1.00, 2.25). Using a higher threshold (3 or 4+ at a 1:160 dilution, 9%) ANA positivity was associated with the carbamate insecticide aldicarb (OR 4.82; 95%CI 1.33, 17.5) and greater combined use of four cyclodiene organochlorine insecticides (top tertile of intensity-weighted lifetime days vs. no use; OR T3 3.20; 95%CI 1.10, 9.27). By contrast, greater use of non-cyclodiene organochlorine insecticides was inversely associated with ANA (1:80 dilution 3 or 4+, OR T3 0.24; 95%CI 0.08, 0.72). Specific autoantibodies (to extractable nuclear antigens and anti-dsDNA), measured on those with ANA detected at the 1:80 dilution 3 or 4+, were seen in 15 individuals (2%), and were associated with use of two or more cyclodiene organochlorine insecticides and several other pesticides (e.g., carbofuran, ethylene dibromide). These findings suggest that specific pesticide exposures may have long-term effects on ANA prevalence and support the hypothesis that certain organochlorine insecticides may increase the risk of developing systemic autoimmunity.
Highlights
Farming occupation and pesticide use have been associated with elevated risk of systemic autoimmune diseases [1,2,3,4,5,6,7,8,9], but the role of specific pesticide exposures in the development of systemic autoimmunity is not known
During follow-up or at Biomarkers of Exposure and Effect in Agriculture (BEEA) enrollment, 44 participants reported an incident diagnosis of an autoimmune disease, which was associated with overall antinuclear autoantibodies (ANA) (Supplemental Table 1)
Our findings provide evidence that moderate to higher level ANA are associated with past use of specific pesticides and a history of seeking medical care for pesticide exposures in male farmers
Summary
Farming occupation and pesticide use have been associated with elevated risk of systemic autoimmune diseases [1,2,3,4,5,6,7,8,9], but the role of specific pesticide exposures in the development of systemic autoimmunity is not known. A few epidemiologic studies have examined ANA in relation to specific agricultural pesticides. In a cross-sectional study of Canadian farmers, ANA prevalence was significantly higher in association with use of some, but not all organochlorine insecticides [15]. In another similar study from the same region, both positive and inverse associations were seen for ANA with the recent use of different herbicides and fungicides, though estimates were imprecise due to small sample size [16]. Other studies have examined serum levels of organochlorine pesticides in relation to ANA, with inconsistent findings [17,18,19]
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