Biol. Stud. 2018: 12(3–4); 103–116 • DOI:


D. V. Maltsev, L. V. Natrus, V. Ye. Kondratiuk, I. E. Degtyarova


Gout is a chronic genetically predisposed inflammatory disease with elevated serum uric acid concentration (hyperuricemia) and subsequent sedimentation in the form of crystals of uric acid mononatric acid in tissues of joints and periarticular zones, vascular walls, skin, and internal organs. Recently, understanding about the mechanism of development of inflammation in gout has deepened, that allows better assess to the state of patient’s severity, to predict the further course of the disease, and to select a rational anti-inflammatory therapy. Due to a refinement of key components of the immunopathogenesis of gout, previously unknown points of application of anti-inflammatory therapeutic interventions were opened and promising prospects for approbation of innovative anti-inflammatory drugs with a new mechanism of action appeared. Nevertheless, a modern concept of mono-stimulated inflammation still requires substantial refinement. This scientific review provides a modern understanding of the events scenario at various stages of the pathological process in the development of gouty inflammation in the joints – initiation, activation of the system of innate immunity, immune inflammation. The most promising molecules that can serve as new biomarkers for estimating patient’s condition and predicting future course of the gout disease, as well as being a target of the therapeutic interventions of anti-inflammatory drugs of subsequent generations, are presented. So, different patterns of immunoreactivity are defined in patients with similar genotype of gout and the level of hyperuricemia, that influence clinical results of disease and are determined by genes’ activation, that control inflammatory reaction in humans body. Discovering such patterns on different stages of disease’s immunopathogenesis and their detailed analyzing due to clinical results is defined as an attractive perspective of optimization of modern approach to clinical case management of patients with hyperuricemia. Examination of polymorphism variants and the level of TLR-2 and TLR-4 genes expression can give another informative immunological biomarker for the estimation of seve­rity of patients condition and predict further course of the gout. disease. Development of new, more effective anti-inflammatory products is very hopeful. That selectively depresses the activity of NALP3-inflamom, TLR-2 and TLR-4 macrophages or regulate the expression rate of the neutrophilic receptors Clec12A and SIRL-1 that are potentially useful for patients of the risk group, which are carriers of the unfavourable variants of key genes associated with a severe course of inflammatory process in joints. Identification of prognosticaly unfavorable variants of genes IL-17 and -22 polymorphism in a risk group of patients with gout can give informative immunological and immunogenetic biomarkers for clinical practice and can allow understanding heterogeneity of clinical course and consequences that occurs in different patients with similar gout genotype and the level of uricemia. The introduction of new monitoring and treatment strategies can optimize control of the immune-inflammatory process in gout, improving quality and prolonging life expectancy of patients.

Keywords: gout, immunopathogenesis, inflammation


1. Busso N., So A. Mechanisms of inflammation in gout. Arthritis Res Ther, 2010; 12(2): 206.
PMid:20441605 PMCid:PMC2888190

2. Cai Y., Peng Y.H., Tang Z. et al. Association of Toll-like receptor 2 polymorphisms with gout. Biomed Rep, 2014; 2(2): 292-296.
PMid:24649113 PMCid:PMC3917755

3. Conforti-Andreoni C., Spreafico R., Qian H.L. et al. Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18. J. Immunol, 2011; 187(11): 5842-5850.

4. Dalbeth N., Clark B., Gregory K. et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann. Rheum. Dis, 2009; 68(8): 1290-1295.

5. Dang W., Xu D., Xie W., Zhou J. Study on the expressions of NLRP3 gene transcript variants in peripheral blood monocytes of primary gout patients Clin. Rheumatol, 2018; 37(9): 2547-2555.

6. Empson V.G., McQueen F.M., Dalbeth N. The natural killer cell: a further innate mediator of gouty inflammation? Immunol Cell Biol, 2010; 88(1): 24-31.

7. Estevez-Garcia I.O., Gallegos-Nava S., Vera-Pérez E. et al. Levels of cytokines and microRNAs in individuals with asymptomatic hyperuricemia and ultrasonographic findings of gout: a bench-to-bedside approach. Arthritis Care Res (Hoboken), 2018 Feb 18.

8. Fernandes M.J., Naccache P.H. The Role of Inhibitory Receptors in Monosodium Urate Crystal-Induced Inflammation. Front Immunol, 2018; 9: 1883.
PMid:30177932 PMCid:PMC6109781

9. Hall C.J., Sanderson L.E., Lawrence L.M. Blocking fatty acid-fueled mROS production within macrophages alleviates acute gouty inflammation. J Clin Invest, 2018; 128(5):1752-1771
PMid:29584621 PMCid:PMC5919807

10. Harre U., Derer A., Schorn C. et al. T cells as key players for bone destruction in gouty arthritis? Arthritis Res Ther, 2011; 13(6): 135.
PMid:22136246 PMCid:PMC3334629

11. Huang Y., Jiang H., Chen Y. et al. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol Med, 2018; 10(4). pii: e8689.
PMid:29531021 PMCid:PMC5887903

12. Jiri M., Zhang L., Lan B. et al. Genetic variation in the ABCG2 gene is associated with gout risk in the Chinese Han population. Clin Rheumatol, 2016; 35(1): 159-163.

13. Kaneko K., Maru M. Determination of urate crystal formation using flow cytometry and microarea X-ray diffractometry. Anal Biochem, 2000; 281(1): 9-14.

14. Kong Y.Y., Feige U., Sarosi I. et al. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature, 1999; 402(6759): 304-309.

15. Liu Y., Zhao Q., Yin Y. et al. Serum levels of IL-17 are elevated in patients with acute gouty arthritis. Biochem Biophys Res Commun, 2018; 497(3): 897-902.

16. Liu-Bryan R. Intracellular innate immunity in gouty arthritis: role of NALP3 inflammasome. Immunol Cell Biol, 2010; 88(1): 20-23.
PMid:19935768 PMCid:PMC4337950

17. Luo C.Y., Wang L., Sun C., Li D.J. Estrogen enhances the functions of CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cell Mol Immunol, 2011; 8(1): 50-58.
PMid:21200384 PMCid:PMC4002989

18. Luo G., Yi T., Zhang G., Guo X., Jiang X. Increased circulating Th22 cells in patients with acute gouty arthritis: A CONSORT-compliant article. Medicine (Baltimore), 2017; 96(42): e8329.
PMid:29049247 PMCid:PMC5662413

19. Martin W.J., Walton M., Harper J. Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout. Arthritis Rheum, 2009; 60(1): 281-289.

20. Martinon F. Detection of immune danger signals by NALP3. J Leukoc Biol, 2008; 83(3): 507-511.

21. Mills K.H., Dungan L.S., Jones S.A, Harris J. The role of inflammasome-derived IL-1 in driving IL-17 responses. J Leukoc Biol, 2013; 93(4): 849-497.

22. Shi Y., Evans J.E., Rock K.L. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature, 2003; 425(6957): 516-521.

23. Siniachenko O.V., Nikolenko Iu.I., Diadyk A.I. et al. The characteristics of the disorders of the immune status in gout patients. Vrach Delo, 1991; (12): 64-66.

24. Tu H.P., Min-Shan K.A., Lee S.S. et al. Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive predictive value for gout. J Hum Genet, 2018; 63(1): 63-70.

25. Wang J., Yang Q., Zhang Q. et al. Invariant Natural Killer T Cells Ameliorate Monosodium Urate Crystal-Induced Gouty Inflammation in Mice. Front Immunol, 2017; 8: 1710.
PMid:29312287 PMCid:PMC5733058

26. Webb R., Jeffries M., Sawalha A.H. Uric Acid Directly Promotes Human T-Cell Activation. Am J Med Sci, 2009; 337(1): 23-27.

27. Zhang Q.B., Qing Y.F., He Y.L. et al. Association of NLRP3 polymorphisms with susceptibility to primary gouty arthritis in a Chinese Han population. Clin Rheumatol, 2018; 37(1): 235-244.
PMid:29214547 PMCid:PMC5754462

28. Zhang Q.B., Qing Y.F., Yin C.C. et al. Mice with miR-146a deficiency develop severe gouty arthritis via dysregulation of TRAF 6, IRAK 1 and NALP3 inflammasome. Arthritis Res Ther, 2018; 20 (1):45.
PMid:29544526 PMCid:PMC5855987

29. Zou Y., Du J., Zhu Y. et al. Associations between the SLC22A12 gene and gout susceptibility: a meta-analysis. Clin Exp Rheumatol, 2018; 36(3): 442-447.

30. Zhou Z., Li X., Li H. et al. Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population. PLoS One, 2016;11(2): e0148082.
PMid:26890073 PMCid:PMC4758639



  • There are currently no refbacks.

Copyright (c) 2018 Studia biologica