Table_3_Exposure to Mild Steel Welding and Changes in Serum Proteins With Putative Neurological Function—A Longitudinal Study.pdf

Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5–95 percentile: 0.2–4.2) and at T2 0.5 (0.1–1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003–0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.

焊工会暴露于高浓度金属颗粒物环境中，此类颗粒物主要成分为铁及锰（Mn）氧化物。金属颗粒物，尤其是含锰的颗粒物，具备神经毒性。本探索性研究采用纵向研究设计，评估了焊接暴露与血清中87种推定神经相关蛋白表达水平之间的关联。研究队列招募自瑞典南部，纳入了从事低碳钢焊接的焊工（n=56）与对照人群（n=67），所有受试者均为男性且无吸烟史，分别在两个时间点（T1、T2）采集样本，两次采样间隔6年。纵向分析（线性混合模型）中得到的关联结果，在另一项横断面研究样本中通过线性回归模型得到进一步验证：该横断面样本纳入仅单次采集样本（T1或T2）的焊工（n=102）与对照人群（n=89）。经呼吸防护措施校正后，焊工的可吸入粉尘中位浓度在T1为0.6 mg/m³（5~95百分位数：0.2~4.2），在T2为0.5 mg/m³（0.1~1.8）。经校正的可吸入锰中位浓度在T2为0.049 mg/m³（0.003~0.314），校正后的可吸入粉尘与可吸入锰之间的斯皮尔曼相关（Spearman）系数rS=0.88。本研究在纵向样本中鉴定出5种在焊工与对照人群间存在差异表达的神经相关蛋白，其中1种（烟酰胺/烟酸单核苷酸腺苷转移酶1，nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1；NMNAT1）在横断面样本中同样呈现差异表达。NMNAT1是一种与阿尔茨海默病（Alzheimer's disease）相关的轴突保护蛋白，在焊工群体中的表达水平较对照人群上调，但未观察到其表达与暴露程度（仅针对焊工：焊接年限、可吸入粉尘浓度、累积暴露量）存在关联。不过，本研究还鉴定出另外5种蛋白，其表达水平与焊接年限在纵向样本与横断面样本中均存在关联（仅针对焊工：粒细胞集落刺激因子GCSF、Ephrin-A4 EFNA4、组织蛋白酶S CTSS、C型凝集素结构域家族6成员CLM6、血管性血友病因子C结构域包含蛋白2 VWC2）。本研究还观察到多种神经相关蛋白的表达水平与年龄及身体质量指数（BMI）存在关联。本研究结果表明，低至中度的焊接烟尘暴露与循环系统中神经相关蛋白的水平变化存在关联。