sPD-L1 as an Early Sentinel of Immune Homeostasis Disruption in Lead-Exposed Workers: A Biomarker Discovery Study

Objectives This study aimed to investigate the impact of occupational lead exposure on plasma soluble Programmed Death-Ligand 1 (sPD-L1) levels in workers and evaluate the potential value of sPD-L1 as an early immunological biomarker for lead exposure. Methods A cross-sectional study was conducted, involving 224 lead-exposed workers from a lead-acid battery factory as the exposed group and 223 non-lead-exposed workers as the control group. Basic information was collected via questionnaires. Blood lead levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), plasma sPD-L1 levels were detected by enzyme-linked immunosorbent assay(ELISA), and oxidative damage markers (T-SOD, GSH, MDA) and a genetic damage marker (γ-H ₂ AX) were analyzed simultaneously. Generalized linear models(GLM) and restricted cubic spline analysis(RCS) were used to analyze the dose-response relationship between blood lead and various indicators. The benchmark dose method(BMD) was used to evaluate and compare the sensitivity of sPD-L1, oxidative damage, and genetic damage markers to lead exposure. Results Plasma sPD-L1 levels were significantly higher in the exposed group than those in the control group. sPD-L1 levels showed a non-linear positive correlation with blood lead concentrations and were positively correlated with T-SOD, MDA, and γ-H ₂ AX. When sPD-L1 abnormality was used as the outcome variable, the benchmark dose lower bound (BMDL) for blood lead was 44.30 µg/L, which was lower than the BMDL for oxidative damage or traditional immune cell abnormalities as outcome variables. Conclusions Low-dose lead exposure can increase plasma sPD-L1 levels, and sPD-L1 is the most sensitive indicator among the studied biomarkers for lead exposure. These findings suggest that plasma sPD-L1 is a potential novel biomarker for immune homeostasis imbalance induced by low-dose lead exposure, with broad application prospects.