High-sensitivity TSLP assay demonstrates a role of TSLP in eosinophilic and non-eosinophilic asthma.

Abstract

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is dysregulated in asthma. Blocking TSLP decreases T2 inflammation and reduces exacerbation rate across patients with T2 high and T2 low asthma. TSLP is a potential biomarker in asthma, but the relationship between levels of TSLP in different compartments and key components of asthma are largely unknown. The aim was to compare serum TSLP in patients (Pt) with asthma and healthy controls (HC) and to examine the relationship between TSLP in serum, sputum, and BAL, and Pt demographics, airway pathophysiology and inflammation. Serum, sputum, and BAL TSLP levels were measured using a novel high-sensitivity S-PLEX human TSLP kit in a cross-sectional study investigating 183 asthma Pts and 44 HCs. Pts had lung function, FeNO, skin prick test, AHR to mannitol, and a blood differential count. A sub-group of Pts had induced sputum (n=71) and a bronchoscopy (n=85) with BAL and mucosa biopsies. The level of serum TSLP (geo.mean fg/ml) was increased in Pts with both non-eosinophilic and eosinophilic asthma compared to HCs (1409.2 and 1772.0 vs 938.8fg/ml, p<0.001). Serum TSLP was higher in men (1717.1 vs 1399.2fg/ml, p=0.004) and was positively associated (rho(s)) with age (0.49, p<0.001) and blood eosinophils (0.35, p<0.001). Levels of TSLP in sputum were associated with AHR (PD15 to mannitol rho(s) -0.39, p=0.001) and BAL TSLP was positively associated with airway submucosal eosinophils (0.34, p=0.002). Using a high-sensitivity assay for measuring TSLP we demonstrated elevated serum levels in eosinophilic and non-eosinophilic asthma and correlations between sputum and BAL TSLP and AHR and eosinophilic airway inflammation.