Assessing the impact of heavy metals and metalloids from soil on blood levels of rheumatoid factor in patients with rheumatoid arthritis

Introduction: Heavy metals can cause disturbances in the functioning of various systems of the human body and play an important role in the development of autoimmune diseases.

Objective: To assess the relationship between heavy metals and metalloids in soil and the level of rheumatoid factor (RF) in adult patients with rheumatoid arthritis living in the Republic of Tatarstan.

Materials and methods: The study included 380 permanent residents of the Republic of Tatarstan diagnosed with rheumatoid arthritis. Soil samples were collected in residential areas of the cases and tested for heavy metal concentrations. Odds ratios were used to establish the relationship between soil concentrations of heavy metals and the levels of rheumatoid factor in the blood of subjects.

Results: Changes in soil levels of heavy metals were found to correlate with those in the levels of rheumatoid factor in the blood of adults with rheumatoid arthritis. Patients with an advanced stage of the disease living in the areas with soil levels of cadmium above 0.7 mg/kg and nickel above 50 mg/kg and having an elevated level of RF were 1.8 (OR = 1.7 CI [1.00: 2.88]) and 2 times more frequent (OR = 2.17 CI [1.06: 4.45]), respectively.

Conclusions: Increased levels of heavy metals in soil provoke changes in immunological parameters in patients with various stages of rheumatoid arthritis. In areas with the elevated geochemical background concentrations of cadmium and nickel, higher levels of rheumatoid factor are observed in patients with advanced rheumatoid arthritis.

1. Savilov ED, Anganova EV, Ilina SV, Stepanenko LA. Technogenic environmental pollution and the public health: Analysis and prognosis. Gigiena i Sanitariya. 2016;95(6):507-512. (In Russ.) doi: 10.18821/0016-9900-2016-95-6-507-512

2. Agadzhanyan NA, Makarova II. Ethnic aspect of adaptative physiology and population morbidity. Ekologiya Cheloveka (Human Ecology). 2014;21(3):3-13. (In Russ.) doi: 10.17816/humeco17248

3. Neira M, Erguler K, Ahmady-Birgani H, et al. Climate change and human health in the Eastern Mediterranean and Middle East: Literature review, research priorities and policy suggestions. Environ Res. 2023;216(Pt 2):114537. doi: 10.1016/j.envres.2022.114537

4. Touil H, Mounts K, De Jager PL. Differential impact of environmental factors on systemic and localized autoimmunity. Front Immunol. 2023;14:1147447. doi: 10.3389/ fimmu.2023.1147447

5. Pollard KM. Environment, autoantibodies, and autoimmunity. Front Immunol. 2015;6:60. doi: 10.3389/fimmu.2015.00060

6. Chen L, Sun Q, Peng S, et al. Associations of blood and urinary heavy metals with rheumatoid arthritis risk among adults in NHANES, 1999–2018. Chemosphere. 2022;289:133147. doi: 10.1016/j.chemosphere.2021.133147

7. Salnikova EV, Burtseva TI, Skalny AV. Regional peculiarities of trace elements in the biosphere and the human body. Gigiena i Sanitariya. 2019;98(2):148-152. (In Russ.) doi: 10.18821/0016-9900-2019-98-2-148-152

8. Paithankar JG, Saini S, Dwivedi S, Sharma A, Chowdhuri DK. Heavy metal associated health hazards: An interplay of oxidative stress and signal transduction. Chemosphere. 2021;262:128350. doi: 10.1016/j.chemosphere.2020.128350

9. Verma N, Sharma R. Bioremediation of toxic heavy metals: A patent review. Recent Pat Biotechnol. 2017;11(3):171- 187. doi: 10.2174/1872208311666170111111631

10. Hybenova M, Hrda P, Procházková J, Stejskal V, Sterzl I. The role of environmental factors in autoimmune thyroiditis. Neuro Endocrinol Lett. 2010;31(3):283-289.

11. Makhnichenko AS, Pashchenko AE. [The influence of heavy metals on the human body.] Science Time. 2016;(2(26)):395- 401. (In Russ.)

12. Arleevskaya M, Takha E, Petrov S, et al. Interplay of environmental, individual and genetic factors in rheumatoid arthritis provocation. Int J Mol Sci. 2022;23(15):8140. doi: 10.3390/ijms23158140

13. Akhmedov KhS. Specific features of the immune status in rheumatoid arthritis in relation to the climatic, geographical, and environmental zones of Uzbekistan. Nauchno-Prakticheskaya Revmatologiya. 2016;54(2):183-186. (In Russ.) doi: 10.14412/1995-4484-2016-183-186

14. Gerlag DM, Raza K, van Baarsen LG, et al. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: Report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis. 2012;71(5):638-641. doi: 10.1136/annrheumdis-2011-200990

15. Takha EA, Larionova RV, Petrov SV, et al. Possible mechanism of the implementing the trigger role of air pollution in rheumatoid arthritis (preliminary data). Gigiena i Sanitariya. 2022;101(2):139-145. (In Russ.) doi: 10.47470/0016-9900-2022-101-2-139-145

16. Petrov SV, Salikhov DG, Elyshev NV. [Levels of heavy metals in soils of the Republic of Tatarstan.] In: The Ecology of the Native Land: Problems and Solutions: Proceedings of the XVII All-Russian Scientific and Practical Conference with international participation, Kirov, April 26–27, 2022. Kirov: Vyatka State University; 2022;1:382-386. (In Russ.)

17. Salikhov DG, Petrov SV, Shamaev ND, et al. An assessment of soil contamination with heavy metals in biogeochemical provinces of the Republic of Tatarstan. Journal of Agriculture and Environment. 2023;(8(36)):2. (In Russ.) doi: 10.23649/JAE.2023.36.8

18. Shuralev EA, Khammadov NI, Osyanin KA, et al. Initial multi-target approach shows importance of improved caprine arthritis-encephalitis virus control program in Russia for hobbyist goat farms. Vet World. 2021;14(7):1718-1726. doi: 10.14202/vetworld.2021.1718-1726

19. Shamaev ND, Shuralev EA, Nikitin OV, et al. Prevalence of Toxoplasma gondii infection among small mammals in Tatarstan, Russian Federation. Sci Rep. 2021;11(1):22184. doi: 10.1038/s41598-021-01582-y

20. Ivanov DV. Heavy metals in soils of the Republic of Tatarstan (an overview). Rossiyskiy Zhurnal Prikladnoy Ekologii. 2015;(4(4)):53-60. (In Russ.)

21. Van Hoovels L, Vander Cruyssen B, Sieghart D, et al. IgA rheumatoid factor in rheumatoid arthritis. Clin Chem Lab Med. 2022;60(10):1617-1626. doi: 10.1515/cclm-2022-0244

22. Peng XC, Yin R, Luo LP, Xu S, Shuai Z. Rheumatoid factor titer as an indicator of the risk of rheumatoid arthritis activity: Dose–effect analysis with the restricted cubic spline model. J Inflamm Res. 2024;17:10699-10709. doi: 10.2147/JIR.S488605

23. Yang TH, Yuan TH, Hwang YH, Lian IB, Meng M, Su CC. Increased inflammation in rheumatoid arthritis patients living where farm soils contain high levels of copper. J Formos Med Assoc. 2016;115(11):991-996. doi: 10.1016/j.jfma.2015.10.001

24. Krasilnikova MS, Sacepina OV. Heavy metals as inductors of autoimmune processes in humans and laboratory animals. Nauchno-Prakticheskaya Revmatologiya. 2007;45(3):54- 58. (In Russ.) doi: 10.14412/1995-4484-2007-689

25. Zhang J, Li C, Zheng Y, Lin Z, Zhang Y, Zhang Z. Inhibition of angiogenesis by arsenic trioxide via TSP-1–TGF-β1- CTGF–VEGF functional module in rheumatoid arthritis. Oncotarget. 2017;8(43):73529-73546. doi: 10.18632/oncotarget.19867

26. Arleevskaya MI, Larionova RV, Brooks WH, Bettacchioli E, Renaudineau Y. Toll-like receptors, infections, and rheumatoid arthritis. Clin Rev Allergy Immunol. 2020;58(2):172-181. doi: 10.1007/s12016-019-08742-z

27. Fabbro SK, Zirwas MJ. Systemic contact dermatitis to foods: Nickel, BOP, and more. Curr Allergy Asthma Rep. 2014;14(10):463. doi: 10.1007/s11882-014-0463-3

28. Chiu LC, Lee CS, Hsu PC, et al. Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: A bicenter observational cohort study. Environ Health. 2024;23(1):29. doi: 10.1186/s12940-024-01070-6

29. Ackland ML, Bornhorst J, Dedoussis GV, et al. Metals in the environment as risk factors for infectious diseases: Gaps and opportunities. In: Nriagu JO, Skaar EP, eds. Trace Metals and Infectious Diseases. Cambridge (MA): MIT Press; 2015:271-308. doi: 10.7551/mitpress/9780262029193.003.0022.