22
In the current study, TMEM178 relative gene expression levels showed significant down regulation in asthmatic children when compared with control. In addition, TMEM178 expression levels decreased significantly with severity of asthma progression. Consistent with our results, Patel et al. 6 stated that TMEM178 expression decreases with the increase severity of asthma giving the known role of TMEM178 as a negative regulator of nuclear factor of activated T-cells (NFAT), they hypothesized that TMEM178 plays a significant role in NFAT-induced severe asthma inflammation.
To estimate the performance characteristics of TMEM178 expression (2^-∆Ct) for asthma severity prediction, the best cut off point for 2-ΔCt of the expressed gene and the responsiveness (sensitivity and specificity) were analyzed, to our knowledge, for the first time. The expression of TMEM178 had a strong potential to predict different asthma phenotypes, indicating that TMEM178 expression may be of considerable use in distinguishing between different asthma phenotypes.23
In the present study, relative gene expression levels of CLCA1, SERPINB2 and Periostin showed statistically significant up regulation in epithelial airway cells of children with asthma, when compared with control. Regarding asthma severity, relative gene expression levels of CLCA1, SERPINB2 and Periostin showed no statistically significant differences between different groups. These results run in accordance with Mertens et al,24 who stated that inflammation of allergic airways in asthma was characterized by signature of an airway epithelial gene consisting of POSTN, CLCA1, and SERPINB2; this gene signature Th2 is suggested as a method for classification of asthma cases into phenotypes Th2- high and Th2-low. Also, Woodruff et al.,8 found that CLCA1, serpinB2 and periostin, were up-regulated in asthmatics compared to healthy control.
Sterk and Lutter 25 found that gene expression for IL13, periostin, and CLCA1 were significantly up regulated in asthmatic patients compared with control subjects. Additionally,Singhaniaet al., 26 found greater expression (up-regulation) of the IL-13 response gene signature (CLCA1, POSTN, SERPINB2) in severe asthmatics compared to healthy controls.
Herein, FKBP5 expression was increased in asthmatic children compared to control, however; the difference didn’t reach the border line of statistical significance. Likewise, FKBP5 showed no statistical variation between different asthma severity groups. In contrast,Singhania et al ., 26reported that FKBP5 was more pronounced in severe asthma relative to healthy controls. In the present study, the asthmatic children were not on nasal or systemic steroid in order to induce FKBP5 expression, which explain this discrepancy.
Regarding to asthma control level, relative gene expression levels of TMEM178, CLCA1, SERPINB2 and Periostin were significantly up regulated in controlled group. While, FKBP5 was significantly increased (up regulated) in partially to uncontrolled group. Woodruff et al.,8 found that the CLCA1, serpinB2 and Periostin were shown to have up-regulated in asthma. Corticosteroid therapy down-regulated expression of those three genes and dramatically up-regulated expression of FKBP51. Although high baseline expression of CLCA1, serpinB2 and Periostin was associated with good clinical response to corticosteroids, a weak response associated with high expression ofFKBP51 . By using cultured airway epithelial cells, they observed that IL-13 improved the CLCA1, Periostin, and serpinB2 expression, an effect that was inhibited by corticosteroids. Taken together, these finding indicate that airway epithelial cells in asthma have a distinct activation profile and recognize direct and cell-autonomous effects on airway epithelial cells relevant to corticosteroid therapy on that relate to treatment responses.
Regarding to atopic status, relative gene expression levels of CLCA1, SERPINB2 and Periostin were significantly up regulated in atopic asthma than non-atopic while there were no statistically significant differences between atopic and non-atopic asthma regarding both TMEM187 and FKBP51 expression levels. In line with our findings, a previous study reported that SERPINB2 gene expression can serve as a back-up marker of Th2-driven inflammation in respiratory epithelial cells which is considered as the main mechanism of atopic asthma pathogenesis.