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.