Clinical and Genetic Study of Chronic Kidney Disease

Author Name(s): Elena V. Nekipelova, Olga N. Novakova, Vladimir F. Kulikovskij, Nina I. Zhernakova, Mikhail I. Churnosov
Author Email: litovkina@bsu.edu.ru

Abstract

This paper presents the results of the study of the interrelationships of polymorphic loci of chemokines (rs1719153, rs4512021, rs2107538, rs2857657, rs1801157) with features of humoral immunity in patients with chronic glomerulonephritis. It was established that the concentration of immunoglobulins A and G in the group of patients with chronic glomerulonephritis was significantly higher than in the control group (p<0.001). It was revealed that the genotype +1931TT CCL4 (rs1719153) is a marker of an increased level of immunoglobulin G in patients with chronic glomerulonephritis (p=0.05).

Introduction

Chronic glomerulonephritis (CGN) holds a special place in the structure of chronic kidney diseases as one of the main causes of terminal renal failure and associated disability and mortality (Litovkina et al., 2014; Sorokina et al., 2016). According to available data, glomerulonephritis is considered as an immunemediated renal disease with diffuse proliferativeexudative lesion of the glomerular apparatus of the kidneys, caused by imbalance of regulatory mechanisms of immunocompetent cells and renal glomerulus cells with the involvement of other components of the kidney tissue in the pathological process (Dudnyk et al., 2015; Nekipelova et al., 2016). Despite the fact that the role of the main classes of immunoglobulins (Ig) in the development of CGN is currently undoubtable, there are relatively few publications devoted to studies of immunoglobulin in CGN, available in the literature. Immunoglobulins are classified as specific humoral immunity factors that specifically recognize a wide variety of antigens, interact with other immunocompetent cells having corresponding receptors, and activate the complement system (Arias et al., 2013). The Ig level in peripheral blood is one of the often tested parameters of the immune system, characterizing the immune status in normal state and in immunopathological disorders (Floccari et al., 2007). Therefore, interest in the study of immunological indicators such as IgA, IgM, IgG is not accidental, but is caused by the desire to evaluate the humoral unit of the immune response in patients with CGN. A diversity of clinical manifestations of CGN, significant differences in the rate of decrease in renal function with the same severity of risk factors allows us to discuss the importance of the genetic component in the formation of a predisposition to this disease and determination of the features of its course. According to modern literature data, among the candidate CGN genes, chemokines are especially prominent (Azmandian et al., 2012). Chemokines are peptide low-molecular immunomodulators with chemoattractant properties (Stangou et al., 2016). They control the migration of different types of leukocytes with the relevant receptors from the bloodstream to the tissues, inflammation and autoimmune process foci, participate in activation and differentiation of leukocytes, angiogenesis, fibrogenesis (Wada, 2008; Eddy, 2014). However, the results of molecular genetic studies of chronic glomerulonephritis of different authors often differ and do not give an unambiguous answer to the question of the pathogenetic role of individual polymorphisms of chemokine genes (Bagci et al., 2015; Dudnyk et al., 2015; Sorokina et al., 2016). The objective of this research was to study the interrelationships of polymorphic loci of chemokines (rs1719153, rs4512021, rs2107538, rs2857657, rs1801157) with features of humoral immunity in patients with chronic glomerulonephritis.

Conclusion

Thus, within the framework of this paper, the study of associations of polymorphic loci of chemokines (rs1719153, rs4512021, rs2107538, rs2857657, rs1801157) with features of humoral immunity in patients with chronic glomerulonephritis, residing in the Central Chernozem Region of Russia, established that the genotype +1931TT CCL4 (rs1719153) with a higher level of immunoglobulin G in patients with chronic glomerulonephritis (p=0.05). It was established that the concentration of immunoglobulins A and G in the group of patients with chronic glomerulonephritis was significantly higher than in the control group (p<0.001).

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