P21 Evaluating the clinical impact of corticosteroid sensitivity and insensitivity of peripheral blood mononuclear cells in severe asthma. (15th November 2017)

• Record Type: Journal Article
• Authors: Thomas, A; Siddiqui, S; Amrani, Y
• Is Part Of: Thorax. Volume 72(2017)Supplement 3
• Page Start: A93
• Page End: A93
• Publication Date: 2017-11-15
• Subjects: Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2017-210983.163
• Languages: English
• ISSNs: 0040-6376

Abstract

Abstract : Steroid insensitivity and the heterogeneous nature of asthma represent a significant clinical challenge for patients with severe asthma. The use of peripheral blood mononuclear cells (PBMC) in recent studies has allowed researchers to demonstrate that poor steroid response could be due to corticosteroid insensitivity in immune cells. These cells have been used as a model to investigate the underlying molecular mechanisms of corticosteroid resistance. These models were however inconclusive and have failed to consider asthma phenotypes. Our aim was to determine in vitro corticosteroid sensitivity of isolated PBMCs in TH 2 high and TH 2 low patients. Severe asthma patients as classified by the Global Initiative for Asthma were recruited and divided into TH 2 high and TH 2 low cohorts based on fractional exhaled nitric oxide (FeNO). Isolated PBMCs were stimulated with αCD3/28 alone or in the presence of dexamethasone (10 -10 M-10 -6 M). IL-5, IL-13 and IL-17 cytokine release were measured using ELISA. Correlation studies were carried out to determine whether the LogIC50 or FeNO correlated with markers of asthma severity. PBMCs stimulated with αCD3/28 showed significant IL-5 and IL-17 release in TH 2 low but not TH 2 high patients. Production of IL-5 or IL-7 was dose-dependently suppressed by dexamethasone with different potencies. IL-13 was only significantly stimulated in TH 2 low patients and did not show suppression by dexamethasone. A significant negative correlation between αCD3/28 stimulated IL-17 production and FeNO was observed. Overall, PBMCs from severe asthmatics retain cell responsiveness to TCR engagement with production of TH 2 and TH 17 cytokines and inhibition by dexamethasone. Additional studies comparing TH 2 high vs TH 2 low patients are required to determine whether differences in in vitro CS response exist between these 2 categories of patients.