Features of the immune profile of workers of a non-ferrous metallurgy enterprise in conditions of contamination of biological media with rare earth elements (using the example of thulium)

Introduction. The active use of rare earth elements, including thulium (Tm), in various technological processes increases the risks of health problems associated with the professional activities of the employee.

The purpose of the study is to study the characteristics of the immune profile of workers at a non-ferrous metallurgy enterprise under conditions of contamination of biological media with rare earth elements (using the example of thulium).

Materials and methods. 35 employees of a non-ferrous metallurgy enterprise were examined. The comparison group consisted of workers with the level of thulium concentration in the blood within the reference interval (n=17), the observation group — workers whose blood thulium content was 2 times higher than the upper limit of the reference values (n=18). The content of thulium in biological media (blood) was studied using mass spectrometry with inductively coupled plasma. Flow cytometry was used to detect Annexin V-FITC⁺7AAD⁺-lymphocytes (late apoptosis/necrosis), enzyme immunoassay — IL6, TNF, general IgE, allergosorbent — specific IgG to lanthanides.

Results. It was found that the workers in the observation group had a 2.3-fold increase in the content of total IgE and a 2.0-fold increase in the expression of specific IgG to lanthanides in relation to the results of the comparison group (p<0.05). It was found that with an excess thulium content in the blood, there is an inhibition of cell death by 15% relative to the values of the comparison group.

Limitations of the study. Limitations of the study relate to the limited sample size.

Ethics. The study protocol was approved by the Biomedical Ethics Committee of the local ethical committee of the Federal Budgetary Institution «FSC MPT URZN» No. 2 dated March 22, 2023. The study was carried out in accordance with the requirements set out in the WMA Declaration of Helsinki «Ethical Principles for Medical Research Involving Human Subjects» (1964, 2013). Voluntary informed consent to participate in the study and use of personal data was signed by all participants.

Contribution:
Dolgikh O.V. — development of the research concept, interpretation of data, editing of the manuscript;
Alekseev V.B. — data interpretation, manuscript editing;
Dianova D.G. — development of the concept and design of research, analysis and interpretation of data, writing the text of the manuscript;
Vdovina N.A. — data collection and processing.

Funding. The research was carried out as part of the research work of R&D No. 121081900044-4, reg. No. ICRBS, and had no funding.

Conflict of interests. The authors declare no conflict of interests.

Received: 18.06.2024 / Accepted: 02.08.2024 / Published: 15.09.2024

1. Brouziotis A.A., Giarra A., Libralato G., Pagano G., Guida M., Trifuoggi M. Toxicity of rare earth elements: An overview on human health impact. Front. Environ. Sci. 2022; 10: 2022. https://doi.org/10.3389/fenvs.2022.948041

2. Sager M., Wiche O. Rare earth elements (REE): origins, dispersion, and environmental implications — a comprehensive review. Environments. 2024; 11(2): 24. https://doi.org/10.3390/environments11020024

3. Pagano G., Guida M., Tommasi F., Oral R. Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects. Ecotoxicol. Environ. Saf. 2015; 115: 40–48. https://doi.org/10.1016/j.ecoenv.2015.01.030

4. Liu H., Liu H., Yang Z., Wang K. Bone mineral density in population long-term exposed to rare earth elements from a mining area of China. Biol. Trace. Elem. Res. 2021; 199(2): 453–464. https://doi.org/10.1007/s12011-020-02165-0

5. Adeel M., Lee J.Y., Zain M., Rizwan М., Nawab А., Ahmad M.A. et al. Cryptic footprints of rare earth elements on natural resources and living organisms. Environment. International. 2019; 127: 785–800. https://doi.org/10.1016/j.envint.2019.03.022

6. Oladipo H.J., Tajudeen Y.A., Taiwo E.O., Muili A.O., Yusuf R.O., Jimoh S.A. et al. Global environmental health impacts of rare earth metals: insights for research and policy making in Africa. Challenges. 2023; 14(2): 20. https://doi.org/10.3390/challe14020020

7. Fleurbaix E., Parant M., Maul A., Cossu-Leguille C. Toxicity of lanthanides on various fish cell lines. Ecotoxicology. 2022; 31: 1147–1157. https://doi.org/10.1007/s10646-022-02574-y

8. Zhang Q., O’Brien S., Grimm J. Biomedical applications of lanthanide nanomaterials, for imaging, sensing and therapy. Nanotheranostics. 2022; 6(2): 184–194. https://doi.org/10.7150/ntno.65530

9. Schubert D., Dargusch R., Raitano J., Chan S.W. Cerium and yttrium oxide nanoparticles are neuroprotective. BBRC. 2006; 342(1): 86–91. https://doi.org/10.1016/j.bbrc.2006.01.129

10. Hanana Н., Turcotte P., Pilote M., Auclair J., Gagnon C. Biomarker assessment of lanthanum on a freshwater invertebrate, Dreissena polymorpha. SOJ Biochemistry. 2017; 3: 9–17. https://doi.org/10.15226/2376-4589/3/1/00120

11. Duosiken D., Yang R., Dai Y., Marfavi Z., Lv Q., Li H., Sun K., Tao K. Near-infrared light-excited reactive oxygen species generation by thulium oxide nanoparticles. J. Am. Chem. Soc. 2022; 144(6): 2455–2459. https://doi.org/10.1021/jacs.1c11704

12. Obitz D., Gkika K.S., Heller M., Keyes T.E., Metzler‑Nolte N.A phototoxic thulium complex exhibiting intracellular ROS production upon 630 nm excitation in cancer cells. ChemComm. 2023; 59(14). https://doi.org/10.1039/D2CC06209G

13. Perry J., Minaei E., Engels E., Ashford B.G., McAlary L., Clark J.R. et al. Thulium oxide nanoparticles as radioenhancers for the treatment of metastatic cutaneous squamous cell carcinoma. Phys. Med. Biol. 2020; 65(21): 215018. https://doi.org/10.1088/1361-6560/abaa5d

14. Rodushkin I., Ödman F., Olofsson R., Burman E., Axelsson M.D. Multi-element analysis of body fluids by double-focusing ICP-MS. Recent Research Developments in Pure & Applied Analytical Chemistry. 2001; 5: 51–66.

15. Zaitseva N.V., Dolgikh O.V., Dianova D.G. Exposure to airborne nickel and phenol and features of the immune response mediated by E and G immunoglobulins. Health Risk Analysis. 2023; 2: 160–168.

16. Lin C., Kadono T., Yoshizuka K., Furuichi T., Kawano T. Effects of fifteen rare-earth metals on Ca2+ influx in tobacco cells. Z. Naturforsch., C: Biosci. 2006; 61(1–2): 74–80. https://doi.org/10.1515/znc-2006-1-214

17. Hou F., Huang J., Qing F., Guo T., Ouyang S., Xie L. et al. The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca2+-CamkII/Ampk axis. Ecotoxicol. Environ. Saf. 2023; 263: 115262. https://doi.org/10.1016/j.ecoenv.2023.115262

18. Sweeney K.J., Han X., Müller U.F. A ribozyme that uses lanthanides as cofactor. Nucleic Acids Res. 2023; 51(14): 7163–7173. https://doi.org/10.1093/nar/gkad513

19. Sojka B., Liskova A., Kuricova M. et al. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes. J. Nanopart. Res. 2017; (19): 68. https://doi.org/10.1007/s11051-017-3779-9

20. Rosa C.P., Belo T.C.A., Santos N.C.M., Silva E.N., Gasparotto J., Corsetti P.P., de Almeida L.A. Reactive oxygen species trigger inflammasome activation after intracellular microbial interaction. Life Sci. 2023; 331: 122076. https://doi.org/10.1016/j.lfs.2023.122076

21. Macharadze D.S. Modern clinical aspects of assessing the levels of total and specific IgE. Pediatrija. 2017; 96 (2): 121–127 (in Russian).