Identification of biomarker sets for predicting the efficacy of sublingual immunotherapy against pollen-induced allergic rhinitis

Abstract

Sublingual immunotherapy (SLIT) is effective against allergic rhinitis, although a substantial proportion of individuals is refractory. Herein, we describe a predictive modality to reliably identify SLIT non-responders (NRs). We conducted a 2-year clinical study in 193 adult patients with Japanese cedar pollinosis, with biweekly administration of 2000 Japanese allergy units of cedar pollen extract as the maintenance dose. After identifying high-responder (HR) patients with improved severity scores and NR patients with unchanged or exacerbated symptoms, differences in 33 HR and 34 NR patients were evaluated in terms of peripheral blood cellular profiles by flow cytometry and serum factors by ELISA and cytokine bead array, both pre- and post-SLIT. Improved clinical responses were seen in 72% of the treated patients. Pre-therapy IL-12p70 and post-therapy IgG1 serum levels were significantly different between HR and NR patients, although these parameters alone failed to distinguish NR from HR patients. However, the analysis of serum parameters in the pre-therapy samples with the Adaptive Boosting (AdaBoost) algorithm distinguished NR patients with high probability within the training data set. Cluster analysis revealed a positive correlation between serum Th1/Th2 cytokines and other cytokines/chemokines in HR patients after SLIT. Thus, processing of pre-therapy serum parameters with AdaBoost and cluster analysis can be reliably used to develop a prediction method for HR/NR patients.

Association of Basophil-Expressing Genes with Effectiveness of Sublingual Immunotherapy

“…RNA of post-SLIT basophils of both groups was assessed in microarray analysis. The peripheral basophil population was unaffected by SLIT, and the population did not differ between HR and NR patients, as described 1 . However, we identified 153 genes that were differentially expressed between HR and NR patients (Fig.…”

“…Twenty-five HR and NR JCP patients were selected from patients who received 2-year SLIT, as described previously 1 . RNA of post-SLIT basophils of both groups was assessed in microarray analysis.…”

“…The study design, patient recruitment, administration of cedar pollen extract, and evaluation of clinical efficacy were performed as described recently 1…”

“…Basophils were purified as CD123 + CD11c low BDCA-1 − BDCA-4 − HLA-DR − cells from peripheral blood, as previously described 1…”

“…However, SLIT does not benefit some patients. We previously compared SLIT nonresponders (NR) and high responders (HR) and identified potential determinants of SLIT efficacy, namely, patients with high correlations among serum Th1/Th2 cytokines tended to respond well to SLIT 1 .…”