Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.
Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, China.
Front Immunol. 2022 Jan 12;12:805404. doi: 10.3389/fimmu.2021.805404. eCollection 2021.
Subcutaneous 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.
We 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.
Sixty-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.
Our 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.
皮下免疫疗法（SCIT）是治疗过敏性鼻炎（AR）儿童的有效方法，但疗效在患者之间存在波动。目前尚无可靠的候选生物标志物用于监测和预测 SCIT 的反应。本研究旨在通过多种细胞因子谱分析，确定用于预测儿童 AR 患者 SCIT 疗效的新型生物标志物。
我们前瞻性招募了 72 例屋尘螨（HDM）诱导的 AR 患儿，他们被分配接受 SCIT。在基线时采集血清样本，并通过 Luminex 检测进行多种细胞因子谱分析。所有患者均随访 1 年，然后根据疗效将其分为有效组和无效组，并比较两组间 48 种选定细胞因子的水平。在一个包含 54 例有效应答者和 26 例无效应答者的队列中，进一步通过酶联免疫吸附试验（ELISA）验证潜在的细胞因子。
72 例患儿中有 69 例完成了 1 年随访计划，其中 46 例患儿归入有效组，23 例归入无效组。细胞因子谱分析结果显示，15 种细胞因子（嗜酸性粒细胞趋化因子、G-CSF、GM-CSF、IFN-γ、IL-12(p40)、IL-13、IL-15、IL-16、IL-4、MIF、MIP-1α、RANTES、SCF、SDF-1α 和 VEGF）在有效组和无效组之间存在差异（均 P<0.05）。未调整和调整后的多变量分析模型突出显示，血清嗜酸性粒细胞趋化因子、IFN-γ、IL-4 和 MIF 水平与儿童 HDM 诱导的 AR 患者 SCIT 的疗效密切相关。此外，受试者工作特征（ROC）曲线揭示了这四个生物标志物在预测 SCIT 反应中的潜在价值。在 80 例儿科患者的队列中进行的进一步 ELISA 验证结果表明，应答者的血清嗜酸性粒细胞趋化因子和 IL-4 水平升高，而应答者的 IFN-γ 水平降低（均 P<0.05）。ROC 曲线表明，血清 IL-4 在预测 SCIT 疗效方面比嗜酸性粒细胞趋化因子和 IFN-γ 更可靠。
我们的发现-验证研究表明，包括 IL-4、嗜酸性粒细胞趋化因子和 IFN-γ 在内的细胞因子可能作为预测儿童 HDM 诱导的 AR 患者 SCIT 反应的有力生物标志物。这些结果进一步证实了细胞因子与 SCIT 反应相关，并有助于了解其潜在的治疗机制。
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