Parks, Jin; Santos, A; Lerro, CC; Dellavalle, CT; Ward, MH; Alavanja, MC; Berndt, SI; Beane Freeman, LE; Sandler, DP; Hofmann, JN
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.
Autoantibodies; Cohort study (or longitudinal study); Epidemiologyâanalytic (risk factors); Occupational epidemiology; Pesticides; 1,2 dibromoethane; aldicarb; aldrin; antinuclear antibody; azathioprine; butylate; campheclor; carbamic acid derivative; carbofuran; chlordane; chlorphenotane; cyanazine; cyclosporine; dieldrin; disease modifying antirheumatic drug; fonofos; heptachlor; hydroxychloroquine; leflunomide; lindane; malathion; methotrexate; methyl bromide; mycophenolate mofetil; nonsteroid antiinflammatory agent; organochlorine insecticide; pesticide; pesticide residue; petroleum; salazosulfapyridine; antinuclear antibody; chlorinated hydrocarbon; pesticide; adult; aged; agricultural worker; Article; autoimmune disease immunofluorescence assay; autoimmunity; body mass; crop production; fluorescence microscopy; follow up; health care survey; HEp-2 cell line; human; human cell; immunofluorescence test; interview; long term exposure; major clinical study; male; middle aged; occupational exposure; prevalence; questionnaire; rheumatoid arthritis; sensitivity analysis; smoking; systemic lupus erythematosus; very elderly; agricultural worker; agriculture; blood; immunology; longitudinal study; occupational exposure; risk factor; Aged; Agriculture; Antibodies, Antinuclear; Autoimmunity; Farmers; Humans; Hydrocarbons, Chlorinated; Longitudinal Studies; Male; Middle Aged; Occupational Exposure; Pesticides; Prevalence; Risk Factors; Surveys and Questionnaires