Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling

Abstract

BackgroundSubcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.MethodsWe prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.ResultsSixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in 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 (all 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 HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.ConclusionOur discover–validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis

“…The sum of total nasal symptom score and final MS was defined as nasal symptom and medication score (SMS). A reduction of SMS by at least 30% compared to baseline level was defined as effective SCIT; otherwise, the SCIT was considered to be ineffective [ 28 ].…”

“…Immunotherapy. SCIT was conducted as previously described [28]. All AR patients received Novo-Helisen Depot (NHD) allergen extracts (Allergopharma, Reinbek, Germany) from Der f and Der p at a 1 : 1 ratio.…”

Exosomes Derived hsa-miR-4669 as a Novel Biomarker for Early Predicting the Response of Subcutaneous Immunotherapy in Pediatric Allergic Rhinitis

“… 1 The participant’s inclusion and exclusion criteria, immunotherapy schedules and efficacy assessment strategy were carried out as our previous study described. 30 Eight patients were allocated to the effective group (n=4) and ineffective group (n=4) for sequencing. The validation was conducted with two independent cohorts.…”

Update on pathomechanisms and treatments in allergic rhinitis

“…A decrease in basophil sensitivity after 3 weeks of treatment predicted long‐term improvement in seasonal combined symptom and medication scores after SCIT treatment 95 . To identify the patients who are more responsive to SCIT, IL‐4, eotaxin, and IFN‐γ might represent robust biomarkers for early prediction of SCIT response in children with HDM‐induced AR 96 …”