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"Child`s Health" 3 (46) 2013

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Clinical and genetic aspects of chronic pyelonephritis in children: the structure of predisposition and primary prognosis

Authors: Kryuchko T.O., Ostapenko V.P., Kushnereva T.V., High State Educational Institution "Ukrainian Medical Stomatological Academy",Poltava, Ukraine.

Categories: Pediatrics/Neonatology

Sections: Clinical researches

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Keywords

innate immunity, polymorphism, Toll-like receptors, bacterial infection, intracellular pathogens.

In recent years there has been increasing the proportion of infections of the urinary system in total morbidity of children. It is known that some of children inclined to a protracted course of acute inflammation, complications and relapse. This category of children deserves special attention, because the frequent infections can lead to basic disruption of compensatory-adaptive mechanisms lead to significant disturbances of the functional state of the body, which reduces immune resistance and lead to early development of chronic diseases. The vast majority of these children inflammation leads to irreversible renal parenchyma damage with replacement of damaged sections of connective tissue, which further leads to the development of chronic renal failure (CRF) and hypertension.

During last years, thanks to the progress of scientific disciplines such as molecular biology, genetics, immunology and cell biology, the accumulation of knowledge about the mechanisms of various infectious diseases, and it becomes possible to accurate diagnosis and prognosis. We know that the state of resistance to infection is formed by numerous reactions of the immune system, which main function is the recognition and elimination of infectious agents and their metabolic products. Toll-like receptors (TLR) have key role among the distinctive receptors of innate immunity.

To date, the role of Toll-like receptors in the development of many infections remains to be unclear and requires detailed researches. Defects in the Toll-like receptors system, such as violations of recognition ligands, expression of TLR, signal transduction, synthesis of effectors molecules and gene polymorphism Toll-like receptors can lead to the development of severe infectious diseases, autoimmune diseases, atherosclerosis, allergic pathology etc. Our attention was caught to polymorphisms TLR4 Asp299Gly, because there are some research that indicate that the presences of these mutant alleles of genes that increase the risk of infection of urogenital infections such as chlamydiosis, mycoplasmosis, ureoplasmosis, hardnelosis, trichomoniasis. As the differences in the genes which control the body's protective response may determine the different nature of the inflammatory response and specific immunological reactions when introducting of foreign agents, the research of the children prevalence single nucleotide substitutions with chronic pyelonephritis (PN) is of particular interest.

The aim of our research was to assess the current position of importance of polymorphism Asp299Gly Toll-like receptor 4 in the implementation of susceptibility to chronic pyelonephritis in childhood and to analyze its association with major pathogens of the urinary system infections.

A clinical and laboratory examination of 53 children with chronic pyelonephritis during exacerbation who were hospitalized in the pediatric department number 2 (Renal beds) Children's Regional Hospital Poltava was conducted. Genotyping polymorphic sites Asp299Gly performed by polymerase chain reaction (PCR) using oligonucleotide primers. 95 healthy individuals with genetic samples from Base Institute Genetic and immune basics of pathology and pharmacogenetics VDNZU "UMSA" were the control group. Bacteriological examination of urine with the establishment of microbial pathogen and its sensitivity to antibiotics and chemotherapeutic agents, and molecular biological studies (polymerase chain reaction to determine Chlamidia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, material research - epithelial scraping cells from the urethra) in most patients were carried out before prescribed of antibiotic therapy.

The analysis of the frequency distribution of genotypes in the researched gene TLR4 Asp299Gly in groups observations showed that the "wild type" genotype TLR4 met in 91.6% of healthy individuals, the frequency of heterozygote genotype was 8.4%, mutant GG - 0,0%. While children with chronic pyelonephritis frequency of genotypes AG and GG almost 2 times higher than the control group results (AG - 13,2% and GG - 1,9%). The research of the prevalence of normal and mutant alleles 299Gly gene Toll-like receptor 4 in the surveyed groups showed that the mutant allele Gly almost 2 times more often detected in children with chronic pyelonephritis (8.4%) compared with the control group (4.21%).

Having the genome of chronic pyelonephritis in children with gene polymorphism Toll-like receptor 4 (TLR4) determined that heterozygote and homozygote for the mutant allele genotypes are associated with increased sensitivity to major intracellular pathogens (Mycoplazma hominis, Ureaplazma ureolyticum) PN.

Thus, our findings indicate that heterozygote and homozygote for the mutant allele genotypes can be considered as predictors of higher risk of chronic pyelonephritis realization, which is associated with increased susceptibility to mycoplasma and ureoplasma infections and formation of phenotypic manifestations of the disease, with a prevalence of recurrent and torpid course of inflammatory changes and the necessity for long-term maintenance uroseptics therapy. The results of the research confirm the important role of Toll-like receptors in the realization of an innate immune response and allow considering polymorphism Toll-like receptor 4 in an additional prognostic indicator in genetic researches.


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