Increased Serum EphA2 is Associated with Disease Severity in Pediatric Patients with Asthma

Asthma is the most prevalent chronic inflammatory airway disease in children, with increasing incidence and prevalence. Ephrin type-A receptor 2 (EphA2) belongs to the Ephrin (Eph) family. It is predominantly found in bronchial epithelial cells and may play a potential role in mediating airway inflammation in asthma. However, this study aimed to evaluate the association between a novel biomarker, EphA2, in two distinct pediatric asthma populations stratified by disease severity.

Serum levels of interleukins (IL-1β, IL-4, IL-6, IL-8, IL-13), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP-2 and MMP-9), and EphA2 were measured by ELISA in all participants. In addition, blood eosinophil counts, Total IgE levels and exhaled nitric oxide (FeNO) levels were evaluated.

Serum EphA2 levels in patients with asthma (n=195) were significantly higher than those in healthy controls (n=120), and the levels were notably elevated in patients with severe asthma (n=82) than in those with mild-moderate asthma (n=113). Receiver Operating Characteristic (ROC) curve analysis revealed that the ideal threshold for serum EphA2 was 324.76 pg/mL. This cutoff point demonstrated a sensitivity of 88.7% and a specificity of 92.5%, yielding an Area Under the Curve (AUC) of 0.959. Further correlative analysis indicated that serum EphA2 level was negatively correlated with forced expiratory volume in 1 second (FEV1) (r=-0.376, P<0.001), the ratio of FEV1 to forced vital capacity (FVC) (r=-0.476, P<0.001), and peak expiratory flow (PEF) (r=-0.699, P<0.001). Furthermore, we observed that serum EphA2 positively correlated with Eosinophil count (r=0.227, P=0.001), Total IgE (r=0.715, P<0.001), FeNO (r=0.560, P<0.001), IL-1β (r=0.423, P<0.001), IL-4 (r=0.314, P<0.001), IL-6 (r=0.625, P<0.001), IL-8 (r=0.628, P<0.001), IL-13 (r=0.569, P<0.001), TNF-α (r=0.562, P<0.001), TGF-β1 (r=0.535, P<0.001), MMP-2 (r=0.273, P<0.001), and MMP-9 (r=0.266, P<0.001) in all asthma patients.

Our research suggests that EphA2 might be a valuable marker for assessing the risk of exacerbation, inflammation of the airways, and airway remodelling in asthma patients.