Associations between exposure to metals, chlorinated pesticides, and PCBs and differential leukocyte profiles in Flemish adolescents

Although environmental pollutants are known to affect the immune system, the impact of chemical mixtures on adolescent immune function remains understudied. Adolescence is a critical period for immune maturation, and disruptions during this stage may have implications for long-term health. Leukocytes, key components of the immune system, serve as indicators of immune status, with altered levels reflecting potential inflammation or immunosuppression. The present study examined the associations of 14 chemical exposure biomarkers measured in blood with counts of total leukocytes and leukocyte subtypes in 980 adolescents (13-16 years old) from the Flemish Environment and Health Studies 2012-2020 (FLEHS III and IV). The exposure biomarkers included 5 metals, 3 chlorinated pesticides, and 6 polychlorinated biphenyls (PCBs). We used four different statistical approaches: multiple linear regression, elastic net, Bayesian model averaging, and Bayesian kernel machine regression. Total leukocyte and neutrophil counts were negatively associated with PCBs and manganese (Mn), and positively associated with copper (Cu), whereas lymphocyte count was negatively associated with thallium (Tl). The neutrophil-lymphocyte ratio (NLR) was also negatively associated with Mn. An analysis excluding smokers additionally showed that higher cadmium (Cd) concentrations were associated with lower leukocyte count. Our study suggests immunosuppressive effects of PCBs, non-essentials metals Tl and Cd, and the essential metal Mn. Due to the cross-sectional design, we cannot rule out the possibility of reverse causation. The current study provides epidemiological evidence that exposure to metals and PCBs may have adverse effects on the immune system at concentrations detected in a general population of adolescents.