Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.
Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.
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DOI：
10.1016/j.rmed.2017.12.002
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发表时间：
2018
影响因子：
4.3
通讯作者：
M. Suzukawa;H. Matsumoto;Nobuharu Ohshima;H. Tashimo;I. Asari;T. Tajiri;A. Niimi;H. Nagase;H. Matsui;N. Kobayashi;S. Shoji;K. Ohta
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文献类型：
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作者：
M. Suzukawa;H. Matsumoto;Nobuharu Ohshima;H. Tashimo;I. Asari;T. Tajiri;A. Niimi;H. Nagase;H. Matsui;N. Kobayashi;S. Shoji;K. Ohta
domalizumab是一种人源化抗ige单克隆抗体，是首个用于治疗严重哮喘的分子靶向药物。然而，患者对omalizumab的反应差异很大。目的：本研究旨在评估基线血清细胞因子水平作为对omalizumab反应性预测因子的潜力。方法31例重度持续性哮喘患者接受奥玛珠单抗治疗至少1年。在治疗48周时，根据医生对治疗效果的总体评估（GETE）评估对omalizumab的反应。在基线和开始使用omalizumab后16周和32周采集血液样本，并通过Luminex 200和ELISA检测30种细胞因子。呼气一氧化氮（FeNO）水平、外周血嗜酸性粒细胞计数、支气管扩张剂前肺功能和哮喘生活质量问卷评分分别在基线和开始奥玛单抗后16、32和48周进行测定。评估前一年和48周奥玛珠单抗治疗期间临床显著哮喘发作的数量。结果gete评估有应答者19例（61.3%），无应答者12例（38.7%）。应答者在基线时的CXCL10和IL-12水平明显高于无应答者（CXCL10：应答者，1530.0±315.2 pg/ml vs.无应答者，1066.0±396.8 pg/ml, P = 0.001； IL-12：应答者，60.2±39.2 pg/ml vs.无应答者，32.2±26.3 pg/ml, P = 0.04）。使用基线血清CXCL10水平区分应答者和无应答者的ROC曲线显示良好的AUC为0.83。在奥玛珠单抗治疗32周时，血清CXCL10趋于升高（基线时为1350±412.3 pg/ml， 32周时为1529±637.6 pg/ml, P = 0.16），血清IL-12趋于降低（基线时为49.4±37.0 pg/ml， 32周时为43.9±30.9 pg/ml, P = 0.05）。另一方面，血清IL-5和PDGF显著降低（IL-5基线为54.2±13.8 pg/ml， 32周时为49.1±12.5 pg/ml, P = 0.008； PDGF基线为4821±2458 pg/ml， 32周时为4219±1951 pg/ml， P = 0.048）。结论高基线血清CXCL10和IL-12水平可能有助于预测奥玛珠单抗对重症哮喘患者的良好反应。
BackgroundOmalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients.ObjectivesThis study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab.MethodsThirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed.ResultsGETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49.1 ± 12.5 pg/ml at 32 weeks, P = 0.008; PDGF: 4821 ± 2458 pg/ml at baseline vs. 4219 ± 1951 pg/ml at 32 weeks, P = 0.048).ConclusionsHigh baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics.