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 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.

bronchial asthma, transcription factors, T-bet, STAT4, STAT6, phenotype

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