T-bet syndrome-associated bronchial asthma phenotype

We aimed to evaluate a significance of T-bet transcription factor in bronchial asthma (BA). A total of 102 patients with BA were examined. The control group was represented by healthy subjects (21 people). The study model was represented by peripheral blood mononuclear cells isolated in a density gr...

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Autores principales:	L. N. Sorokina, V. N. Mineev, A. V. Eremeeva, M. A. Nyoma
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	bronchial asthma transcription factors t-bet stat4 stat6 phenotype Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6775d45ccf494302bc2e9095e5336e5b
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spelling	oai:doaj.org-article:6775d45ccf494302bc2e9095e5336e5b2021-11-18T08:03:49ZT-bet syndrome-associated bronchial asthma phenotype1563-06252313-741X10.15789/1563-0625-TSB-1874https://doaj.org/article/6775d45ccf494302bc2e9095e5336e5b2020-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1874https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XWe aimed to evaluate a significance of T-bet transcription factor in bronchial asthma (BA). A total of 102 patients with BA were examined. The control group was represented by healthy subjects (21 people). The study model was represented by peripheral blood mononuclear cells isolated in a density gradient with standard method. It was found that some patients were characterized by high levels of transcription factor T-bet expression (T-bet > 1.0). The bronchial asthma patients with increased T-bet expression were moir often characterized by the severe disease, requiring therapy with systemic glucocorticoids and β2-agonists, did not have genetic predisposal for allergic diseases, the majority of them had excess body weight and concomitant morbidity (mainly, cardiovascular, gastrointestinal and endocrine disorders). The study of rs324011 polymorphism of STAT6 protein gene in these patients revealed CC and CT genotypes, mostly observed in severe BA. Moreover, they were observed in 100% patients with severe clinical course of BA. A positive correlation was found between the number of T allele presentation in loci, and BA severity (r = 0.88, p = 0.002), as well as between the distribution by genotype (CC-CT/TT), and absolute (counts per one L), and relative (%) number of eosinophils in the sputum (r = 0.79, p = 0.034). The detected associations may be referred to as “T-bet elevation syndrome”, being based on the phenomenon of “genetically determined heterogeneity of signaling system defects”. In individuals with an increased T-bet expression, a significant elevation of transcription factors STAT6 and STAT4 was also detected. Taken together, the presented data indicate that this phenomenon reflects a disturbance of the Th1 / Th2 balance, due to increase in both Th1 and Th2 transcriptional activity. Thus, the patients with bronchial asthma with increased expression of T-bet transcription factor revealed a symptom complex, which we have called “T-bet elevation syndrome” (T-bet > 1.0), which is characterized mainly by severe disease and a certain phenotype of patients. Most likely, this feature is caused by genetically determined defects of signaling systems. High T-bet expression has been observed in young patients with mild BA and can be a prognostic sign.L. N. SorokinaV. N. MineevA. V. EremeevaM. A. NyomaSPb RAACIarticlebronchial asthmatranscription factorst-betstat4stat6phenotypeImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 1, Pp 181-186 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	bronchial asthma transcription factors t-bet stat4 stat6 phenotype Immunologic diseases. Allergy RC581-607
spellingShingle	bronchial asthma transcription factors t-bet stat4 stat6 phenotype Immunologic diseases. Allergy RC581-607 L. N. Sorokina V. N. Mineev A. V. Eremeeva M. A. Nyoma T-bet syndrome-associated bronchial asthma phenotype
description	We aimed to evaluate a significance of T-bet transcription factor in bronchial asthma (BA). A total of 102 patients with BA were examined. The control group was represented by healthy subjects (21 people). The study model was represented by peripheral blood mononuclear cells isolated in a density gradient with standard method. It was found that some patients were characterized by high levels of transcription factor T-bet expression (T-bet > 1.0). The bronchial asthma patients with increased T-bet expression were moir often characterized by the severe disease, requiring therapy with systemic glucocorticoids and β2-agonists, did not have genetic predisposal for allergic diseases, the majority of them had excess body weight and concomitant morbidity (mainly, cardiovascular, gastrointestinal and endocrine disorders). The study of rs324011 polymorphism of STAT6 protein gene in these patients revealed CC and CT genotypes, mostly observed in severe BA. Moreover, they were observed in 100% patients with severe clinical course of BA. A positive correlation was found between the number of T allele presentation in loci, and BA severity (r = 0.88, p = 0.002), as well as between the distribution by genotype (CC-CT/TT), and absolute (counts per one L), and relative (%) number of eosinophils in the sputum (r = 0.79, p = 0.034). The detected associations may be referred to as “T-bet elevation syndrome”, being based on the phenomenon of “genetically determined heterogeneity of signaling system defects”. In individuals with an increased T-bet expression, a significant elevation of transcription factors STAT6 and STAT4 was also detected. Taken together, the presented data indicate that this phenomenon reflects a disturbance of the Th1 / Th2 balance, due to increase in both Th1 and Th2 transcriptional activity. Thus, the patients with bronchial asthma with increased expression of T-bet transcription factor revealed a symptom complex, which we have called “T-bet elevation syndrome” (T-bet > 1.0), which is characterized mainly by severe disease and a certain phenotype of patients. Most likely, this feature is caused by genetically determined defects of signaling systems. High T-bet expression has been observed in young patients with mild BA and can be a prognostic sign.
format	article
author	L. N. Sorokina V. N. Mineev A. V. Eremeeva M. A. Nyoma
author_facet	L. N. Sorokina V. N. Mineev A. V. Eremeeva M. A. Nyoma
author_sort	L. N. Sorokina
title	T-bet syndrome-associated bronchial asthma phenotype
title_short	T-bet syndrome-associated bronchial asthma phenotype
title_full	T-bet syndrome-associated bronchial asthma phenotype
title_fullStr	T-bet syndrome-associated bronchial asthma phenotype
title_full_unstemmed	T-bet syndrome-associated bronchial asthma phenotype
title_sort	t-bet syndrome-associated bronchial asthma phenotype
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/6775d45ccf494302bc2e9095e5336e5b
work_keys_str_mv	AT lnsorokina tbetsyndromeassociatedbronchialasthmaphenotype AT vnmineev tbetsyndromeassociatedbronchialasthmaphenotype AT averemeeva tbetsyndromeassociatedbronchialasthmaphenotype AT manyoma tbetsyndromeassociatedbronchialasthmaphenotype
_version_	1718422355404914688

T-bet syndrome-associated bronchial asthma phenotype

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