Multiple-Cytokine Profiling: A Novel Method for Early Prediction of the Efficacy of Sublingual Immunotherapy in Allergic Rhinitis Patients

Abstract

Background Allergic rhinitis (AR) is a common inflammatory airway disease, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for it. However, not all AR patients respond to AIT, and early prediction of patient response is extremely important. This study aimed to example serum levels of multiple cytokines in AR and explore their association with the efficacy of AIT. Methods A total of 74 AR patients treated with sublingual immunotherapy (SLIT) were prospectively recruited. Serum samples were obtained before the onset of SLIT and cytokine levels detected by multiplex analysis. All patients were followed for >1 year, and associations between cytokine levels and the early efficacy of SLIT were evaluated. Significantly distinctive cytokines were further verified in another independent cohort. Results Sixty patients completed the visit schedule set: 35 patients were put into a responder group and 25 a nonresponder group. Multiple-cytokine profiling showed that cytokine levels differed significantly between the two groups. The responder group had higher concentrations of BAFF and CCL11 and lower levels of CCL2, CCL7, IFNγ, IL8, IL10, IL16, and IL33 than the nonresponder group ( P <0.05). Receiver-operating characteristic curves highlighted that serum BAFF, IFNγ, IL10, and IL33 levels were strongly predictive of the efficacy of SLIT (area under the curve <0.7, P <0.05). Serum IL10 and IL33 were overexpressed in nonresponders in the validation cohort. Patients in the responder group exhibited significantly higher IL10 levels and lower IL33 post-SLIT than pre-SLIT ( P <0.05), but no statistical difference was found in nonresponders ( P <0.05). Conclusion Our data indicated that serum multiple-cytokine profiling was associated with response to SLIT and that IL10 and IL33 might serve as novel biomarkers for early prediction of efficacy and be involved in the therapeutic mechanisms of SLIT in AR patients.

Allergic Rhinitis: A Clinical and Pathophysiological Overview

“…High serum periostin levels were observed after HDM-SLIT, indicating that serum periostin appears to be a useful biomarker in AIT ( 109 ). Furthermore, multiple cytokines profiling was investigated in treated AR patients with SLIT where serum BAFF, IFNγ, IL10, and IL33 levels were strongly predictive of the efficacy of SLIT ( 110 ). These sets of biomarkers are closely associated with Th1 immune response and type 2 innate lymphoid cells downstream signaling pathway in AR.…”

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis

“…33 In a study with 1-year follow-up, baseline S100A11 concentrations were found to predict the effectiveness of sublingual AIT, with an AUC of 0.76, in patients with AR. 34 Furthermore, in a randomized, open-label controlled trial, Hoshino et al reported that serum periostin levels could distinguish sublingual AIT responders from nonresponders in adult AR patients allergic to HDM, with a cutoff value of 30.2 ng/mL and an AUC of 0.79. 35 However, it is important to note that these previous studies have primarily focused on individual immune markers.…”

The Impact of Cytokines on Health-Related Quality of Life in Adolescents with Allergic Rhinitis

“…Additionally, allergic inflammation is linked with a shift in the ratio of Th1 to Th2 cell production of cytokines towards a Th2 predominance [45]. Due to natural allergen exposure, Th2 lymphocytes proliferate with the release of cytokines such as IL-1, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-18 and GM-CSF, and these inflammatory mediators play important roles in the pathogenesis of AR [46][47][48]. In the present study, the flow cytometrybased immunofluorescent assay kit was used to detect the levels of human cytokines in nasal mucosa IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33 in adolescents with AR with different severity of the disease.…”