Identification Of Robust Biomarkers For Early Predicting Efficacy Of Subcutaneous Immunotherapy In Children With Allergic Rhinitis By Multiple Cytokine Profiling

Background: Subcutaneous immunotherapy(SCIT)is one of the effective treatments for children with allergic rhinitis(AR),but its efficacy is different among patients.There are no reliable biomarkers for monitoring and predicting the response to SCIT.The goal of this study is to identify novel biomarkers for early predicting the efficacy of SCIT in children with AR patients based on multiple cytokine profiling.Methods: We prospectively recruited 72 pediatric AR patients who were assigned to receive SCIT.The serum samples were collected and then multiple cytokine profiling was conducted by Luminex assay at baseline.All patients were followed-up for 1 year and then classified into effective and ineffective group based on their efficacy,and 48 cytokines levels were analyzed between two groups.The potential cytokines were further evaluated by enzyme-linked immunosorbent assay(ELISA)in a validation cohort with 54 responders and 26 non-responders.Results: Sixty-nine children completed the following-up schedule,and 46 of them were classified into effective group and 23 patients were into ineffective group.The results of multiple cytokine profiling showed that 15 cytokines(Eotaxin,G-CSF,GM-CSF,IFN-γ,IL-12(p40),IL-13,IL-15,IL-16,IL-4,MIF,MIP-1α,RANTES,SCF,SDF-1α and VEGF)were dysregulated between effective and ineffective group(P < 0.05).Unadjusted and adjusted multivariate analysis models highlighted that serum Eotaxin,IFN-γ,IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric AR patients.In addition,receiver operating characteristic(ROC)curves revealed potential values of these four biomarkers in predicting the response to SCIT.Further ELISA results in the validation cohort demonstrated that serum Eotaxin and IL-4 levels were elevated in responders,and IFN-γ levels were decreased in responders(P < 0.05).ROC curves demonstrated that serum IL-4exhibited more reliable accuracy in predicting SCIT efficacy than Eotaxin and IFN-γ.Conclusion: Our discover–validation study identified several cytokines which may serve as robust biomarkers for early predicting response of SCIT in children with AR.These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.