Background: New anti-IL-5 antibodies, mepolizumab and benralizumab, have recently been approved for severe asthma, sharing the same inclusion criteria. Objective: To contribute on biomarkers research leading to the personalized choice, we investigated L-selectin, Krebs von den Lungen (KL-6), and lymphocyte subsets as bioindicators of airway hyper-responsiveness and remodeling. Materials and Methods: A cohort of 28 patients affected by severe eosinophilic asthma were treated with anti-IL-5 drugs. According to clinical parameters, patients were subdivided into early and partial responders. Lymphocytes subsets were analyzed through flow cytometry, while KL-6 and sL-selectin were analyzed on serum samples. Clinical, functional, and immunological data at baseline (T0), after 1 month (T1), and 6 months of therapy were collected in a database. Results: All treated patients showed an increase in the percentage of forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity ratio and a decrease of peripheral eosinophils for both drugs after 1 month of treatment. Mepolizumab-treated patients also showed decreased CD8⁺ and NKT-like cell percentages and a significant increase in sL-selectin concentrations between T0 and T1. Stratifying the cohort of our patients in early and partial responders at T0, they showed a reduction of peripheral eosinophils, sL-selectin and KL-6, while no differences were found at T0 between early and partial responders patients treated with benralizumab. Conclusions: This real-life study provides new insights for the personalized approach to severe asthma therapy. Although preliminary, the results indicate that besides eosinophils, KL-6 and sL-selectin are useful as biomarkers of early response that can also involve in the pathogenesis of severe asthma.
Int Arch Allergy Immunol

中文翻译：

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美泊珠单抗和贝那珠单抗治疗的重度嗜酸性哮喘患者的个性化方法。

背景：新的抗IL-5抗体美泊珠单抗和贝那珠单抗最近被批准用于重度哮喘，具有相同的纳入标准。目的：为促进导致生物标志物个性化选择的生物标志物的研究，我们研究了L-选择素，Krebs von den Lungen（KL-6）和淋巴细胞亚群作为气道高反应性和重塑的生物指标。材料和方法：用抗IL-5药物治疗28例严重嗜酸性粒细胞性哮喘患者。根据临床参数，将患者分为早期和部分反应者。通过流式细胞仪分析淋巴细胞亚群，同时对血清样品分析KL-6和sL-选择素。在数据库中收集了基线（T0），治疗1个月（T1）和6个月后的临床，功能和免疫学数据。结果：所有接受治疗的患者在治疗1个月后均显示出第一秒钟的强制呼气量百分比（FEV1）和FEV1 /强制肺活量比增加，并且外周嗜酸性粒细胞减少。美泊珠单抗治疗的患者还显示CD8 ⁺降低和NKT样细胞百分比，以及T0和T1之间的sL-选择素浓度显着增加。对T0早期和部分缓解的患者队列进行了分层，结果显示外周血嗜酸性粒细胞，sL-选择素和KL-6减少，而贝那利珠单抗治疗的早期和部分缓解患者在T0时无差异。结论：这项真实的研究为个性化重症哮喘治疗方法提供了新见解。尽管是初步的，但结果表明除嗜酸性粒细胞外，KL-6和sL-选择素还可用作早期反应的生物标志物，其也可能参与严重哮喘的发病机理。
Int Arch过敏免疫