Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients

Rationale Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (u PAR / PLAUR ) have been associated with lung function decline and u PAR blood levels in asthma subjects. Preliminary studies have identified u PAR elevation in asthma; however, a definitive study regarding which clinical features of asthma u PAR may be driving is currently lacking. Objectives We aimed to comprehensively determine the u PAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate u PAR expression to asthma clinical features. Methods uPAR levels were determined in control ( n = 9) and asthmatic ( n = 27) bronchial biopsies using immunohistochemistry, with a semi‐quantitative score defining intensity in multiple cell types. Soluble‐cleaved (sc) u PAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts. Measurements and main results In bronchial tissue, u PAR was elevated in inflammatory cells in the lamina propria ( P = 0.0019), bronchial epithelial ( P = 0.0002) and airway smooth muscle cells ( P = 0.0352) of patients with asthma, with u PAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scu PAR serum levels were elevated in patients with asthma (1.5‐fold; P = 0.0008), and we identified an association between high u PAR serum levels and severe, nonatopic disease. Conclusions This study provides novel data that elevated airway and blood u PAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.