IMMUNOGENETIC PARAMETERS IN PATIENTS AFTER ENDOPROSTHETICS OF LARGE JOINTS AND THEIR SIGNIFICANCE IN PREDICTING THE DEVELOPMENT OF PERIPROSTHETIC INFECTION

The aim of the study is to determine the relationships between immunogenetic parameters in patients after endoprosthetics of large joints with primary osteoarthritis and to identify prognostic criteria for the development of periprosthetic infection.
Materials and methods. The study included 182 unrelated patients of middle (45–59) and elderly (60–74) age with primary osteoarthritis of large joints stage III who underwent total joint arthroplasty. Group 1 (n = 92) – patients with uncomplicated course. Group 2 (n = 90) – patients with development of periprosthetic infection. Control group – 92 practically healthy individuals. Research methods: clinical; laboratory (immunological – determination of IL-2, IL-4, IL-6, IL-17A, TNFα, IFNγ; genetic – polymorphism of the gene IL-2 (T330G), IL-4 (C589T), IL-6 (C174G), IL-17A (G197A), TNFα (G308A)); instrumental (radiography). Statistical processing of the research results was carried out using the IBM SPSS Statistics Version 25.0 software package (IBM, USA).
Results. The normalized importance was 54,2% for the IL-2 gene SNP (T330G), 100% for the IL-4 gene SNP (C589T), 24,5% for the IL-6 gene SNP (C174G), 13,7% for the IL-17A gene SNP (G197A), and 59,6% for the TNFα gene SNP (G308A). The prediction accuracy of the prognostic model was 97,3%, sensitivity 96,7%, specificity 97,8%, p < 0.001.
Conclusion. The interactions of immunogenetic indicators revealed the prognostic value of determining the SNP of genes of immunoregulatory molecules in predicting periprosthetic infection in patients after endoprosthetics of large joints in primary osteoarthritis, without a significant decrease in the significance of the prognosis, both in the complex (IL-4 (C589T) x TNFα (G308A) x IL-17A (G197A) x IL-2 (T330G) x IL-6 (C174G), and in their more simplified interactions – IL-4 (C589T) x TNFα (G308A) and IL-4 (C589T) x TNFα (G308A) x IL-2 (T330G).

1. Clinical guidelines of the Ministry of Health of the Russian Federation. Coxarthrosis. URL: https://cr.minzdrav.gov.ru/preview-cr/870_1 (accessed: 01.11.2025). In Russian.

2. Clinical guidelines of the Ministry of Health of the Russian Federation. Gonarthrosis. URL: https://cr.minzdrav.gov.ru/preview-cr/868_1 (accessed: 01.11.2025). In Russian.

3. Lyubimova L.V., Pavlova S.I., Nikolaev N.S. et al. Possibility of using synovial C-reactive protein, interleukin-6 and presepsin in the diagnosis of periprosthetic infection. Traumatology and Orthopedics of Russia. 2024. 30 (4). 5–13. doi: 10.17816/2311-2905-17578. In Russian.

4. Guder C., Gravius S., Burger C., Wirtz D.C., Schildberg F.A. Osteoimmunology: a current update of the interplay between bone and the immune system. Front. Immunol. 2020. 11 (58). 19. doi: 10.3389/fimmu.2020.00058.

5. Chmielewski M., Pilloni A. Current molecular, cellular and genetic aspects of peri-implantitis disease: a narrative review. Dent J (Basel). 2023. 11 (5). 134. doi: 10.3390/dj11050134.

6. Crawley F.P. Declaration of Helsinki: Full paragraph-by-paragraph comparison indicating changes in version 19 October 2024 compared with the most previous version of 19 October 2013. Zenodo, 2024. URL: https://doi.org/10.5281/zenodo.13997192 (date of access: 01.11.2025).

7. McNally M., Sousa R., Wouthuyzen-Bakker M. et al. The EBJIS definition of periprosthetic joint infection. Bone Joint J. 2021. 103-B (1). 18–25. doi: 10.1302/0301-620X.103B1.BJJ-2020-1381.R1.

8. Mudrov V.A. Algorithms for statistical analysis of biomedical research data using the SPSS software package (in accessible language). Moscow: Logosfera. 2022. 143. ISBN 9785986570884. In Russian.

9. Miromanov A.M., Yeshidorzhiev D.A., Mironova O.B., Miromanova N.A. The significance of the interleukin-4 gene SNP–589C>T and the tumor necrosis factor-alpha gene–308G>A in the pathogenesis of periprosthetic infection in patients after large joint restoration with primary osteoarthritis. Transbaikalian Medical Bulletin. 2025. 3. 73-84. doi: 10.52485/19986173_2025_3_73. In Russian.

10. Miromanov A.M., Gusev K.A., Staroselnikov A.N., Mudrov V.A. Prediction of impaired consolidation of limb long-bone fractures using neural network analysis. Genij Ortopedii. 2025. 31 (2). 237–244. doi: 10.18019/1028-4427-2025-31-2-237-244.

11. Vasconcelos D.M., Ribeiro-da-Silva M., Mateus A. et al. Immune response and innervation signatures in aseptic hip implant loosening. J. Transl. Med. 2016. 14 (1). 205. doi: 10.1186/s12967-016-0950-5.

12. Sendi P., Müller A.M., Berbari E. Are all joints equal? Synovial fluid analysis in periprosthetic joint infection. J. Bone Jt. Infect. 2018. 3. 258–9. doi: 10.7150/jbji.30491.

13. Crotti T.N., Dharmapatni A.A., Alias E., Haynes D.R. Osteoimmunology: major and costimulatory pathway expression associated with chronic inflammatory induced bone loss. J. Immunol. Res. 2015. 2015. 281287. doi: 10.1155/2015/281287.

14. Jones D., Glimcher L.H., Aliprantis A.O. Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection. J. Clin. Invest. 2011. 121 (7). 2534–42. doi: 10.1172/JCI46262.

15. Garcia-Moreno M., Jordan P.M., Günther K. et al. Osteocytes serve as a reservoir for intracellular persisting Staphylococcus aureus due to the lack of defense mechanisms. Front. Microbiol. 2022. 13. 937466. doi: 10.3389/fmicb.2022.937466.

16. Brandt S.L., Putnam N.E., Cassat J.E., Serezani C.H. Innate immunity to Staphylococcus aureus: evolving paradigms in soft tissue and invasive infections. J. Immunol. 2018. 200 (12). 3871–3880. doi: 10.4049/jimmunol.1701574.

17. Sridharan R., Cameron A.R., Kelly D.J., Kearney C.J., O’Brien F.J. Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Materials Today. 2015. 18. 313–25. doi: 10.1016/j.mattod.2015.01.019.

18. Zondervan R.L., Vaux J.J., Blackmer M.J., Brazier B.G., Taunt C.J. Improved outcomes in patients with positive metal sensitivity following revision total knee arthroplasty. J. Orthop. Surg. Res. 2019. 14. 182. doi: 10.1186/s13018-019-1228-4.