Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma

Abstract

The prevalence of bronchial asthma has shown its steady increase in the world in recent years. Despite all the achievements of Allergology, control of the disease can be achieved only in two-thirds of patients even if all social risk factors and the influence of concomitant diseases are excluded. Thus, it is necessary to study endogenous factors that modify the pathogenesis of the disease. Toll-like receptors are the main molecules for recognizing pathogenic patterns in the human immune system. Since any Allergy is a recognition error, mutation of the genes of the recognizing molecules can have a direct and multidirectional effect on the nature of the inflammation and its clinical manifestations in bronchial asthma (BA). To detect this effect, 65 patients with BA were examined, and mutations of Toll-like receptor genes were detected: TLR2-Arg753Glu, TLR4- Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G, lymphocyte subpopulations CD3, CD19, CD4, CD8, CD16, phagocytosis indicators, levels of IgA, IgM, IgG, IgE and IL-6, IL-7, IL-9. The assessment of the severity of asthma and its level of control were conducted according to clinical recommendations of the Ministry of health of the Russian Federation in 2019 criteria. We have shown characteristic clinical manifestations of the studied mutations. A lighter course of the disease, more complete control over it and a better response to therapy were found in single-nucleotide substitutions in the Toll-like receptor 4 and 9 (TLR4-Asp299Gly, TLR4-Ghr399Ile, TLR9-T1237C, TLR9-A2848G). On the contrary, a heavier course and a worse response to therapy were detected in the TLR2 mutation with Arg753Glu replacement. In the studied groups, the features of immunity indicators characteristic of genotypes with a lighter and more controlled course of BA were determined: a higher absolute number of T-helpers, with multidirectional changes in the number of T-killers, but with invariably preserved higher ratio of CD4/CD8 in such genotypes. Higher levels of phagocytosis indicators (primarily characterizing chemotaxis) and IL-7, IL-9 were also detected. The exception is the TLR9-A2848G mutation, in which greater disease control and better response to therapy are combined with no changes in the studied laboratory characteristics. At the same time, a specific feature of the genotype of the studied patients with BA was revealed – a combination of Toll-like receptors 4 and 9 mutations. This suggests the presence of genetic patterns that characterize groups of patients with BA that differ in severity, response to therapy, and degree of control, which makes it possible to personalize approaches to diagnosis, prevention, and therapy of the disease.

Keywords

• тoll-like receptors
• asthma
• children
• signaling molecules
• immune status