Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, United States.
Institute in Collective Health Studies, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Front Immunol. 2019 Jul 11;10:1476. doi: 10.3389/fimmu.2019.01476. eCollection 2019.
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 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 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.
农业和农药的使用与系统性自身免疫性疾病有关，虽然某些有机氯杀虫剂和其他农药被怀疑会影响风险，但特定农药在系统性自身免疫发展中的作用尚不清楚。我们在研究生物标志物暴露和农业效应（BEEA；2010-2013 年）中的 668 名男性农民中通过 Hep-2 细胞免疫荧光法测量血清抗核自身抗体（ANA），这是农业健康研究（AHS）的一个亚队列。我们研究了 ANA 与首次在 AHS 登记（1993-1997 年）时报告的 46 种农药的终生使用情况之间的关系，并通过 BEEA 登记进行了定期更新。在调整年龄、州、教育程度、采血季节、当前农药使用和相关农药后，估计了比值比（OR）和 95%置信区间（CI）。具有 ANA 抗体（在 1:80 稀释度时为 3 或 4+强度，占研究参与者的 21%）与因接触农药而寻求医疗护理的报告史（OR 2.15；95%CI 1.17,3.95）、使用熏蒸剂甲基溴（OR 3.16；95%CI 1.05,9.5）和使用石油油/馏分（OR 1.50；95%CI 1.00,2.25）有关。使用更高的阈值（在 1:160 稀释度时为 3 或 4+，占 9%）ANA 阳性与氨基甲酸酯类杀虫剂涕灭威（OR 4.82；95%CI 1.33,17.5）和四种环二烯有机氯杀虫剂的联合使用量更大（强度加权终生日的最高三分位与无使用相比；OR 3.20；95%CI 1.10,9.27）有关。相比之下，非环二烯有机氯杀虫剂的使用量增加与 ANA 呈负相关（在 1:80 稀释度时为 3 或 4+，OR 0.24；95%CI 0.08,0.72）。在 ANA 在 1:80 稀释度时检测到 3 或 4+的那些人，检测到了特定的自身抗体（针对可提取核抗原和抗 dsDNA），在 15 个人（2%）中可见，与使用两种或更多种环二烯有机氯杀虫剂和其他几种农药（例如，涕灭威、二溴乙烯）有关。这些发现表明，特定的农药暴露可能对 ANA 的患病率有长期影响，并支持某些有机氯杀虫剂可能会增加发展为系统性自身免疫的风险的假设。
