High serum cytokine levels may predict the responsiveness of patients with severe asthma to benralizumab
High serum cytokine levels may predict the responsiveness of patients with severe asthma to benralizumab
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DOI：
10.1080/02770903.2021.1942039
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发表时间：
2021-06
影响因子：
1.9
通讯作者：
S. Watanabe;M. Suzukawa;H. Tashimo;Nobuharu Ohshima;I. Asari;S. Imoto;N. Kobayashi;S. Tohma;T. Nagase;K. Ohta
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文献类型：
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作者：
S. Watanabe;M. Suzukawa;H. Tashimo;Nobuharu Ohshima;I. Asari;S. Imoto;N. Kobayashi;S. Tohma;T. Nagase;K. Ohta
摘要目的：Benralizumab是一种抗人IL-5受体α的人源化单克隆抗体，可有效治疗嗜酸性粒细胞重度哮喘。然而，患者对贝那利珠单抗的反应差异很大。在这项研究中，我们的目的是确定一种新的血清生物标志物，以准确预测贝那利珠单抗的反应。方法：17例重度嗜酸粒细胞性哮喘患者入组本那利珠单抗治疗。采集血样;在基线和治疗1、2、4和6个月后进行肺功能检查并发放问卷。测量血液细胞因子水平。缓解定义为治疗4个月后1 s用力呼气量较基线至少升高10.4%。结果：有9名受访者和8名非受访者。无应答者的基线血清干扰素-γ、白细胞介素（IL）-4、-5、-6、-7和-12 p70、IL-17/IL-17 A、IL-17 E/IL-25、IL-18/IL-1F 4、趋化因子（C-C基序）配体（CCL）3/巨噬细胞炎性蛋白（MIP）-1α; CCL 4/MIP-1β; CCL 11/嗜酸性粒细胞趋化因子;基质金属蛋白酶-12;肿瘤坏死因子-α和胸腺基质淋巴细胞生成素水平。贝那利珠单抗给药后，应答者血清CCL 3/MIP-1α和CCL 11/eotaxin水平显著且持续升高（CCL 3/MIP-1α，应答者：144.5 ± 37.9 pg/ml（基线）vs. 210.3 ± 59.4 pg/ml（4个月），p = 0.009;无应答者：270.8 ± 139.8 pg/ml（基线）vs. 299.5 ± 159.9 pg/ml（4个月），p = 0.33; CCL 11/嗜酸性粒细胞趋化因子，应答者：167.9 ± 62.6 pg/ml（基线）对比326.7 ± 134.4 pg/ml（4个月），p = 0.038;无应答者：420.9 ± 323.1 pg/ml（基线）对比502.1 ± 406.0 pg/ml（4个月），p = 0.30）。结论：低基线血清炎性细胞因子水平可能有助于预测良好的贝那利珠单抗反应。本文的补充数据可在www.tandfonline.com/ijas上在线获得。
Abstract Objective: Benralizumab, a humanized monoclonal antibody against human IL-5 receptor alpha, is effective in treating eosinophilic severe asthma. However, patients’ response to benralizumab varies widely. In this study, we aimed to identify a new serum biomarker to accurately predict benralizumab response. Methods: Seventeen benralizumab-treated patients with severe eosinophilic asthma were enrolled. Blood samples were collected; pulmonary function tests were performed and questionnaires were disseminated at baseline and after 1, 2, 4, and 6 months of treatment. Blood cytokine levels were measured. Response was defined as an elevation in forced expiratory volume in 1 s of at least 10.4% from baseline after 4 months of treatment. Results: There were nine respondents and eight non-respondents. The non-responders showed significantly higher baseline serum interferon-γ; interleukin (IL)-4, -5, -6, -7, and -12p70; IL-17/IL-17A; IL-17E/IL-25; IL-18/IL-1F4; chemokine (C-C motif) ligand (CCL)3/macrophage inflammatory protein (MIP)-1α; CCL4/MIP-1β; CCL11/eotaxin; matrix metalloproteinase-12; tumor necrosis factor-α, and thymic stromal lymphopoietin levels. After benralizumab administration, the serum CCL3/MIP-1α and CCL11/eotaxin levels significantly and persistently increased in the responders (CCL3/MIP-1α, responders: 144.5 ± 37.9 pg/ml (baseline) vs. 210.3 ± 59.4 pg/ml (4 months), p = 0.009; non-responders: 270.8 ± 139.8 pg/ml (baseline) vs. 299.5 ± 159.9 pg/ml (4 months), p = 0.33; CCL11/eotaxin, responders: 167.9 ± 62.6 pg/ml (baseline) vs. 326.7 ± 134.4 pg/ml (4 months), p = 0.038; non-responders: 420.9 ± 323.1 pg/ml (baseline) vs. 502.1 ± 406.0 pg/ml (4 months), p = 0.30). Conclusion: Low baseline serum inflammatory cytokine levels may be useful in predicting a good benralizumab response. Supplemental data for this article is available online at at www.tandfonline.com/ijas .