Immunological aspects of patho­genesis of gout in light of recent scientific discoveries as a key for development of informative biomarkers and innovative therapeutic strategies

Abstract

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