College of Public Health and Human Sciences, Oregon State University, Milam Hall, Room 101, Corvallis, OR, 97331, USA.
Oregon Health and Sciences University, Portland, OR, USA.
Environ Health. 2020 Apr 10;19(1):41. doi: 10.1186/s12940-020-00592-z.
Many populations are exposed to arsenic, lead, and manganese. These metals influence immune function. We evaluated the association between exposure to single and multiple metals, including arsenic, lead, and manganese, to humoral immunity as measured by antibody concentrations to diphtheria and tetanus toxoid among vaccinated Bangladeshi children. Additionally, we examined if this association was potentially mediated by nutritional status.
Antibody concentrations to diphtheria and tetanus were measured in children's serum at age 5 (n = 502). Household drinking water was sampled to quantify arsenic (W-As) and manganese (W-Mn), whereas lead was measured in blood (B-Pb). Exposure samples were taken during pregnancy, toddlerhood, and early childhood. Multiple linear regression models (MLRs) with single or combined metal predictors were used to determine the association with antibody outcomes. MLR results were transformed to units of percent change in outcome per doubling of exposure to improve interpretability. Structural equation models (SEMs) were used to further assess exposure to metal mixtures. SEMs regressed a latent exposure variable (Metals), informed by all measured metal variables (W-As, W-Mn, and B-Pb), on a latent outcome variable (Antibody), informed by measured antibody variables (diphtheria and tetanus). Weight-for-age z-score (WFA) at age 5 was evaluated as a mediator.
Diphtheria antibody was negatively associated with W-As during pregnancy in MLR, but associations were attenuated after adjusting for W-Mn and B-Pb (- 2.9% change in diphtheria antibody per doubling in W-As, 95% confidence interval [CI]: - 7%, 1.5%). Conversely, pregnancy levels of B-Pb were positively associated with tetanus antibody, even after adjusting for W-As and W-Mn (13.3%, 95% CI: 1.7%, 26.3%). Overall, null associations were observed between W-Mn and antibody outcomes. Analysis by SEMs showed that the latent Metals mixture was significantly associated with the latent Antibody outcome (β = - 0.16, 95% CI: - 0.26, - 0.05), but the Metals variable was characterized by positive and negative loadings of W-As and B-Pb, respectively. Sex-stratified MLR and SEM analyses showed W-As and B-Pb associations were exclusive to females. Mediation by WFA was null, indicating Metals only had direct effects on Antibody.
We observed significant modulation of vaccine antibody concentrations among children with pregnancy and early life exposures to drinking water arsenic and blood lead. We found distinct differences by child sex, as only females were susceptible to metal-related modulations in antibody levels. Weight-for-age, a nutritional status proxy, did not mediate the association between the metal mixture and vaccine antibody.
许多人群都接触砷、铅和锰等金属。这些金属会影响免疫功能。我们评估了孟加拉国儿童在接种疫苗后，暴露于单一和多种金属（包括砷、铅和锰）与体液免疫（以破伤风类毒素和白喉类毒素抗体浓度衡量）之间的关联。此外，我们还研究了这种关联是否可能受到营养状况的影响。
在儿童 5 岁时（n=502）测量血清中的破伤风类毒素和白喉类毒素抗体浓度。采集家庭饮用水样本以定量测定砷（W-As）和锰（W-Mn），而血液中的铅则用 B-Pb 进行测量。在妊娠、幼儿期和儿童早期采集暴露样本。使用多元线性回归模型（MLR）对单一或综合金属预测因子进行分析，以确定与抗体结果的关联。将 MLR 结果转换为单位，以便于解释，即每增加一倍暴露，抗体结果的变化百分比。结构方程模型（SEM）用于进一步评估金属混合物的暴露情况。SEM 将由所有测量的金属变量（W-As、W-Mn 和 B-Pb）告知的潜在暴露变量（Metals）回归到由测量的抗体变量（破伤风类毒素和白喉类毒素）告知的潜在结果变量（Antibody）。还评估了 5 岁时的体重与年龄比值（WFA）作为中介。
在 MLR 中，妊娠期间的 W-As 与白喉类毒素抗体呈负相关，但在调整了 W-Mn 和 B-Pb 后，相关性减弱（W-As 每增加一倍，白喉类毒素抗体减少 2.9%，95%置信区间[CI]：-7%，1.5%）。相反，妊娠期间的 B-Pb 水平与破伤风类毒素抗体呈正相关，即使在调整了 W-As 和 W-Mn 后也是如此（13.3%，95%CI：1.7%，26.3%）。总体而言，W-Mn 与抗体结果之间呈零关联。通过 SEM 分析表明，潜在的金属混合物与潜在的抗体结果显著相关（β=-0.16，95%CI：-0.26，-0.05），但金属变量的特征是 W-As 和 B-Pb 分别具有正负荷和负负荷。基于性别的 MLR 和 SEM 分析表明，W-As 和 B-Pb 关联仅存在于女性中。体重与年龄比值的中介作用呈零，这表明金属仅对抗体具有直接影响。
我们观察到，儿童在妊娠和生命早期接触饮用水砷和血液铅后，疫苗抗体浓度出现显著变化。我们发现，由于只有女性对金属相关的抗体水平变化敏感，因此按性别存在明显差异。体重与年龄比值（营养状况的一个指标）不能介导金属混合物与疫苗抗体之间的关联。
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