Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.
Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.
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通过多重细胞因子分析鉴定稳健的生物标志物，用于早期预测屋尘螨诱发的过敏性鼻炎儿童皮下免疫治疗的疗效
DOI：
10.3389/fimmu.2021.805404
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发表时间：
2021
影响因子：
7.3
通讯作者：
Jiang W
中科院分区：
文献类型：
--
作者：
Xie S;Fan R;Tang Q;Cai X;Zhang H;Wang F;Xie S;Gao K;Zhang J;Xie Z;Jiang W
背景皮下免疫疗法(SCIT)是治疗儿童变应性鼻炎(AR)的有效方法，但其疗效因患者而异。目前还没有可靠的候选生物标志物来监测和预测对SCIT的反应。本研究旨在寻找新的生物标志物，用于早期预测儿童变应性鼻炎患者SCIT的疗效。方法前瞻性招募72例屋尘螨(HDM)致变应性鼻炎(AR)患儿，接受SCIT治疗。采集血清样本，采用Luminex比色法进行多种细胞因子分析。所有患者均随访1年，根据疗效分为有效组和无效组，检测48种细胞因子水平，并进行比较。在54名应答者和26名无应答者的队列中，通过酶联免疫吸附试验(ELISA)进一步验证了潜在的细胞因子。结果72例患儿中69例完成1年随访，有效组46例，无效组23例。多项细胞因子分析结果显示，有效组与无效组之间有15种细胞因子(嗜酸性粒细胞集落刺激因子、粒细胞集落刺激因子、粒细胞集落刺激因子、干扰素-γ、IL-12(P40)、IL-13、IL-15、IL-16、IL-4、MIF、MIP-1α、RANTES、干细胞因子、SDF-1α和血管内皮生长因子)表达异常(P均<0.05)。未调整和调整的多因素分析模型显示，血清嗜酸性粒细胞趋化因子、干扰素-γ、IL-4和巨噬细胞因子水平与儿童HDM诱导的AR患者的SCIT疗效密切相关。此外，受试者工作特征(ROC)曲线揭示了这四种生物标志物在预测SCIT疗效方面的潜在价值。对80例儿科患者进行的进一步的ELISA法验证结果显示，应答者的血清嗜酸性粒细胞趋化因子和IL-4水平升高，而干扰素-γ水平降低(均P<；0.05)。ROC曲线显示，血清IL-4较嗜酸粒细胞趋化因子和干扰素-γ更能准确预测慢性粒细胞白血病的疗效。结论IL-4、嗜酸性粒细胞趋化因子、干扰素-γ等细胞因子可作为预测HDM致变应性鼻炎早期疗效的生物标志物。这些结果加强了细胞因子与SCIT反应相关的证据，并有助于理解其潜在的治疗机制。
Background 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. Methods 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. Results 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. Conclusion 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.
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影响因子：
7.3
作者：
Montamat G;Leonard C;Poli A;Klimek L;Ollert M
通讯作者：
Ollert M
影响因子：
81.5
作者：
Bousquet, Jean;Anto, Josep M.;Toppila-Salmi, Sanna
通讯作者：
Toppila-Salmi, Sanna
影响因子：
2.6
作者：
Komlosi, Zsolt Istvan;Kovacs, Nora;Akdis, Cezmi A.
通讯作者：
Akdis, Cezmi A.
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影响因子：
2.5
作者：
Bao, Yixiao;Chen, Jianjun;Zhang, Luo
通讯作者：
Zhang, Luo
影响因子：
4.6
作者：
Liu, Wenlong;Zeng, Qingxiang;Luo, Renzhong
通讯作者：
Luo, Renzhong