Elevated serum OX40L is a biomarker for identifying corticosteroid resistance in pediatric asthmatic patients

BACKGROUND: Corticosteroids are widely used to control asthma symptoms, but steroid resistance (SR) is a common adverse reaction. Therefore, it is important to accurately predict the corticosteroid response of asthmatic patients. This study aims to evaluate the serum OX40 ligand (OX40L) in pediatric asthmatic patients, and to investigated its correlations with clinical characteristics and corticosteroid response. METHODS: A total of 192 pediatric asthmatic patients with inhaled corticosteroid (ICS) therapy and 130 healthy controls were selected. Clinical data were collected, and the serum levels of immunoglobulin (IgE), interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), and OX40L were measured by enzyme-linked immunosorbent assay (ELISA). The level of serum OX40L was compared between the steroid-sensitive asthma (SSA) and steroid-resistant asthma (SRA) groups. RESULTS: The serum OX40L level in asthmatic patients (713.5 ± 165.7 pg/mL) was significantly higher than that of the healthy controls (238.6 ± 27.8 pg/mL) (P < 0.001), and significantly higher in SRA group (791.2 ± 167.9 pg/mL) than in SSA group (655.6 ± 138.8 pg/mL) (P < 0.001). The serum OX40L level showed a significant positive correlation with serum IgE, blood percentages of eosinophils and neutrophils, serum IL-6 and TSLP, and showed a negative correlation with asthma control test (ACT) score and forced expiratory volume in first second (FEV1%). Receiver operating characteristics (ROC) curve was performed to obtain a cutoff value of serum OX40L as 780 pg/mL (sensitivity = 58.5%; specificity = 86.4%), which can identify SRA in asthmatic patients. Multivariate logistic regression analysis showed that elevated serum OX40L (≥780 pg/mL), as well as lymphocytes (%), ACT score, serum IL-6 and TSLP, were independent predictors of SRA (OX40L ≥ 780 pg/mL: odds ratio = 4.188; 95% CI = 1.800–9.746; P = 0.001). The serum OX40L level was decreased after ICS treatment in asthmatic patients, and the reduction in serum OX40L was significant higher in SSA group compared with SRA group. CONCLUSION: High serum OX40L can be used as a biomarker to identify asthmatic patients with corticosteroid resistance, and the change in OX40L level also reflects the response to ICS treatment. These results suggest an association of OX40L with the pathophysiology, inflammation, and clinical outcomes of asthma. New agents targeting OX40L can provide more precise and personalized therapy for asthma.