Peripheral Multiple Cytokine Profiles Identified CD39 as a Novel Biomarker for Diagnosis and Reflecting Disease Severity in Allergic Rhinitis Patients

Abstract

Background. Allergic rhinitis (AR) is a common clinical problem, and immune cells and cytokines were proven to be pivotal in its pathogenesis. Our aim is to measure the peripheral concentrations of multiple cytokines in AR patients and identify novel biomarkers for diagnosis and disease severity. Methods. Peripheral blood samples were collected from 50 AR patients, including 25 mild AR (MAR) patients and 25 moderate-severe AR patients (MSAR), and 22 healthy controls (HCs), and multiple cytokine profiling was outlined by Luminex assay. Cytokine levels were compared among the three groups, and their correlations with disease severity were evaluated. The candidate cytokines were further verified by enzyme-linked immunosorbent assay (ELISA) in a validation cohort. Results. Multiple cytokine profiling revealed that CD39 and interferon (IFN)-γ levels were reduced, and interleukin (IL)-13, IL-5, IL-33, and thymic stromal lymphopoietin (TSLP) levels were elevated in the AR group than the HC group ( $P<0.05$ ). Receiver operating characteristic (ROC) curves presented that serum CD39 and IL-33 exhibited strong diagnostic abilities, and serum CD39 and IL-10 presented capacities in distinguishing disease severity ( $AUC>0.8$ , $P<0.05$ ). Moreover, CD39 concentrations were decreased, and IL-10, IL-5, and TSLP concentrations were enhanced in the MSAR group more than in the MAR group. Correlation analysis results showed that serum CD39, IL-5, and TSLP levels were associated with total nasal symptom score (TNSS) and visual analogue score (VAS) ( $P<0.05$ ). Further data in the validation cohort suggested that serum CD39 levels were reduced, and IL-5 and TSLP levels were increased in AR patients, especially in MSAR patients ( $P<0.05$ ). ROC results revealed potential values of serum CD39 in diagnosis and disease severity evaluation in AR patients ( $P<0.05$ ). Conclusion. This study highlighted that peripheral multiple cytokine profiles were significantly varied in AR patients and associated with disease severity. The results in discover–validation cohorts implied that serum CD39 might serve as a novel biomarker for diagnosing AR and reflecting its disease severity.