Lifetime pesticide use and antinuclear antibodies in male farmers from the Agricultural Health Study

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 (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. Moderate to high level ANA (3 or 4+ intensity, 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). High level ANA (3 or 4+, 1:160, 9%) was also 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 versus 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 moderate to high level ANA (OR T3 0.24; 95%CI 0.08, 0.72). Specific autoantibodies (to extractable nuclear antigens and anti-dsDNA), measured on those with moderate to high level ANA, 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.