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

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. Th...

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Autores principales:	E. N. Suprun, E. B. Nagovitsyna, N. I. Kuderova, S. V. Suprun, O. A. Lebed’ko
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	тoll-like receptors asthma children signaling molecules immune status Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8ca4d1c5d9684eee9a656bd65fd950f2
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spelling	oai:doaj.org-article:8ca4d1c5d9684eee9a656bd65fd950f22021-11-18T08:03:50ZSome groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma1563-06252313-741X10.15789/1563-0625-SGO-2049https://doaj.org/article/8ca4d1c5d9684eee9a656bd65fd950f22020-12-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/2049https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThe 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.E. N. SuprunE. B. NagovitsynaN. I. KuderovaS. V. SuprunO. A. Lebed’koSPb RAACIarticleтoll-like receptorsasthmachildrensignaling moleculesimmune statusImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 5, Pp 915-924 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	тoll-like receptors asthma children signaling molecules immune status Immunologic diseases. Allergy RC581-607
spellingShingle	тoll-like receptors asthma children signaling molecules immune status Immunologic diseases. Allergy RC581-607 E. N. Suprun E. B. Nagovitsyna N. I. Kuderova S. V. Suprun O. A. Lebed’ko Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
description	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.
format	article
author	E. N. Suprun E. B. Nagovitsyna N. I. Kuderova S. V. Suprun O. A. Lebed’ko
author_facet	E. N. Suprun E. B. Nagovitsyna N. I. Kuderova S. V. Suprun O. A. Lebed’ko
author_sort	E. N. Suprun
title	Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
title_short	Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
title_full	Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
title_fullStr	Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
title_full_unstemmed	Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
title_sort	some groups of toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/8ca4d1c5d9684eee9a656bd65fd950f2
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Some groups of Toll-like receptor gene polymorphisms and their clinical and pathogenetic manifestations in children with bronchial asthma

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