Heavy Metal Cadmium Pollution Reduces the Cd14 + Subset of Blood Cells in a Chinese Population

Background: Cadmium exposure is increasingly prevalent, especially in many developing countries, such as China. Studies have demonstrated that cadmium exposure poses a large public health threat. However, evidence for early health damage in response to cadmium exposure is still scant. Methods: We first conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3,390 participants above 18 years of age were selected with cluster sampling from three districts in the Hunan region. After demographic information and blood test data were collected, a total of 3,283 subjects who met the inclusion criteria were eligible for inclusion. To screen for early health damage associated with cadmium before clinical diagnosed disease, we further excluded the individuals with hypertension, hyperlipidemia and diabetes as well as smokers and alcohol users and a total of 1,393 individuals remained. To determine which subsets of monocyte exhibit the most dramatic changes in response to cadmium exposure, 1,393 individuals were divided by plasma cadmium levels into quarters and 15 subjects were selected from the lowest and highest quartiles for single-cell RNA sequencing (scRNA-seq). Furthermore, we randomly enrolled 260 individuals from 780 subjects without chronic diseaes in Shimen district from January to March 2019 in the prospective validation study. Immunofluorescence staining for detecting CD14+ cells was performed in peripheral blood mononuclear cells (PBMCs) among the recruited individuals. Findings: From August 2016 to July 2017, 3,283 individuals were enrolled in the cross-sectional study. The median plasma and urine cadmium levels were 0·11 μg/L and 3·94 μg/L, respectively· Among all the blood cell types examined, only the monocyte percentage was negatively associated with plasma cadmium levels (coefficient =-0·11, P=0·048) in the multivariable linear regression analysis. ScRNA-seq analysis revealed that the CD14+ monocyte subset had the most predominant reduction in the highest quartile of cadmium exposure. Both the PBMC smear analysis and flow cytometry showed that the number of CD14+ monocytes decreased significantly in subjects in the highest cadmium quartile. In the validation study, the proportion of circulating CD14+ monocytes was also negatively associated with plasma cadmium levels (coefficient =-0·09, P=0·047) by the multivariable linear regression model. Interpretation: Cadmium exposure-associated alterations in the peripheral blood cell profile imply its effect on systemic immune surveillance and inflammatory function. This study demonstrates that the number of CD14+ monocytes is negatively associated with cadmium exposure levels and that these monocytes constitute a potential early marker for monitoring cadmium-induced health damage. Funding Statement: National Science and Technology Project (No 2015FY111100) and the National Natural Science Foundation of China (No 81470535, 81570451, 81770403, 81870171, and 81800393). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study complied with the Declaration of Helsinki, and the ethical committee of the Xiangya Hospital of Central South University and School of Public Health of Tongji Medical College of Huazhong University of Science and Technology approved the research protocol. Informed consent was obtained from the subjects or their legally authorized representatives.