Objective To investigate the effects of mixed metal exposure on serum complement C3 and C4 levels in school-age children and to assess the immunotoxicity of metal pollutants.

Methods Two hundred and fifty school-age children aged 12-15 years from a city in eastern China were selected as the subjects. The urinary metal/metalloid (hereinafter referred to as "metal") concentration was measured using inductively coupled plasma mass spectrometry, and serum C3 and C4 levels using an automatic biochemical analyzer. Analyses were performed for 16 metals with detection rates greater than 90%. The effects of single metal exposure on complements were analyzed by multiple linear regression, and the effects of mixed metal exposure by elastic net regression, Bayesian kernel machine regression (BKMR), and quartile g-computation regression.

Results It was found by the linear regression model analysis that serum C4 increased by 4.51% for every 0.36 μmol/mol creatinine increase in urinary lead (false discovery rate FDR=0.047), and serum C4 decreased by 5.44% for every 20.06 μmol/mol creatinine increase in urinary arsenic (FDR=0.035). In the effect analysis of mixed exposure, the elastic net regression identified the metals with a high correlation with serum C3 as manganese, nickel, tungsten, and lead, and the metals with a high correlation with serum C4 as nickel, arsenic, strontium, and lead. The BKMR results showed that the serum C3 concentration tended to be higher but not statistically different with increasing mixed exposure, and the serum C4 concentration was significantly lower. The quantile g-computation regression showed that serum C3 levels were not statistically different from mixed metal exposure (P=0.812), and serum C4 levels (ln conversion) decreased by 0.041 with every 25% increase in mixed exposure (ln conversion) (95% confidence interval: -0.079 to -0.002, P=0.042). Urinary arsenic contributed the most to the reduction in serum C4 concentrations in mixed exposure, followed by urinary nickel.

Conclusion Exposure to mixed metals is able to cause reductions in serum C4 levels in children. Arsenic and nickel are key components on the reduction in serum complement levels.