Environmental chemical-wide associations with immune biomarkers in the US: A cross-sectional analysis

Exposure to environmental chemicals influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical exposome. Thus, a comprehensive analysis of the effects across multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemicals and immune biomarkers. We analyzed the United States cross-sectional National Health and Nutrition Examination Survey (NHANES 1999-2018). Chemicals were measured in blood or urine (198 chemicals, 17 families). Immune biomarkers included percentages of lymphocytes, neutrophils, monocytes, basophils, and eosinophils, and counts of red blood cells, white blood cells, and mean corpuscular volume. We conducted survey-weighted, multivariable linear regressions of log2-transformed chemicals on immune measures, adjusted for age, sex, race/ethnicity, poverty-income ratio, waist circumference, cotinine concentration, creatinine for urinary chemicals, and survey cycle. We accounted for multiple comparisons using a false discovery rate (FDR). Among 45,528 adult participants, using survey weights, the mean age was 45.7 years, 51.4% were female, and 69.3% were Non-Hispanic White. There were 65 chemicals associated with white blood cell count. For example, a doubling in the concentration of blood lead was associated with a decrease of 61 white blood cells per L (95% CI: 23-99; FDR=0.005). 122 (61.6%) chemicals were associated with at least one of the eight immune biomarkers. Chemicals in the Metals family were associated with all eight immune measures. Concentrations of a wide variety of biomarkers of exposure to chemicals such as metals and smoking-related compounds, were highly associated with immune system biomarkers, with implications for immune function and toxicology. This environmental chemical-wide association study identified chemicals from multiple families for further toxicological and epidemiological investigation.