Clinical study of relationship between granulocyte activation, HDAC2 and severe asthma

Abstract

Objective To investigate the relationships between granulocyte activation markers, HDAC2 expression and severe asthma, and to explore the biomarkers for the early prediction and identification of severe asthma. Methods The myeloperoxidase(MPO), matrix metalloproteinase 9(MMP-9), neutrophil elastase(NE) and eosinophil cationicprotein(ECP) levels of serum granulocyte activation markers were detected by enzyme linked immunosorbent assay(ELISA), the activity of peripheral blood mononuclear cells(PBMCs) HDAC2 was detected by the Western-blot.Compared each index of severe asthma group with the relevant index of mild-and-moderate asthma group and healthy control group and statistical analysis. Results ①The concentration of granulocyte activation markers MPO [(102.43±28.19) μg/L], MMP-9[(992.97±176.44) ng/L], NE [(9.40±0.99) μg/L] and ECP [(232.85±48.37) μg/L] of severe asthma subjects were significantly higher than that in mild-and-moderate asthma subjects [MPO, MMP-9, NE and ECP were as follows: (48.56±8.78) μg/L, (554.35±99.03) ng/L, (8.01±1.27) μg/L, (105.30±26.93) μg/L, P 0.05). ②The HDAC2 activity (HDAC2/GAPDH: 0.19±0.09) in severe asthma group was significantly lower than that in mild-and-moderate asthma group (0.60±0.08) and healthy control group (1.09±0.26), the difference was statistical significantly (P<0.05). HDAC2 activity in mild-and-moderate asthma group was lower than that in healthy control group, and the difference was statistical significantly (P<0.05). ③The level of MPO, MMP-9, NE and ECP were significantly negatively correlated with FEV1%pred, and the difference was significant (r values were -0.60, -0.75, -0.43 and -0.67, respectively, P<0.01). And a significantly negatively correlated with FEV1/FVC, the difference was significant (r values were -0.52, -0.60, -0.42 and -0.50, respectively, P<0.05). There was also a significant negative correlation between ACT and the concentration of MPO, MMP-9, NE and ECP (r values were -0.69, -0.67, -0.50 and -0.70, respectively, P<0.01). ④There was a significant positive correlation between FEV1%pred, FEV1/FVC and the expression of HDAC2, and the difference was marked in the bilateral Pearson test (r values were 0.68 and 0.61, respectively, P<0.01). A significant positive correlation between HDAC2 activity and ACT was observed (r=0.68, P<0.01). Conclusions The elevation of serum levels of the MPO, MMP-9, NE and ECP in patients with severe asthma indicated the activation in neutrophil and eosinophilic granulocytes, and was significantly higher than that in patients with mild-and-moderate asthma.The activity of PBMCs HDAC2 in severe asthma group was decreased markedly, implying the possibility of the decrease of glucocorticoid sensitivity, and poor therapeutic effect in severe asthma. Key words: Severe asthma; Granulocyte activation; Histone deacetylase 2