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瑞利珠单抗与嗜酸性粒细胞性哮喘:离精准医学更近一步了吗?

Reslizumab and Eosinophilic Asthma: One Step Closer to Precision Medicine?

作者信息

Varricchi Gilda, Senna Gianenrico, Loffredo Stefania, Bagnasco Diego, Ferrando Matteo, Canonica Giorgio Walter

机构信息

Division of Clinical Immunology and Allergy, Department of Translational Medical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy; Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.

Asthma Center and Allergy Unit, Verona University, General Hospital , Verona , Italy.

出版信息

Front Immunol. 2017 Mar 10;8:242. doi: 10.3389/fimmu.2017.00242. eCollection 2017.

Abstract

Human eosinophils represent approximately 1% of peripheral blood leukocytes. However, these cells have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophilic inflammation is present in a significant proportion of patients with severe asthma. Asthma is a chronic inflammatory disorder that affects more than 315 million people worldwide, with 10% having severe uncontrolled disease. Although the majority of patients can be efficiently treated, severe asthmatics continue to be uncontrolled and are at risk of exacerbations and even death. Interleukin-5 (IL-5) plays a fundamental role in eosinophil differentiation, maturation, activation and inhibition of apoptosis. Therefore, targeting IL-5 is an appealing approach to the treatment of patients with severe eosinophilic asthma. Reslizumab, a humanized anti-IL-5 monoclonal antibody, binds with high affinity to amino acids 89-92 of IL-5 that are critical for binding to IL-5 receptor α. Two phase III studies have demonstrated that reslizumab administration in adult patients with severe asthma and eosinophilia (≥400 cells/μL) improved lung function, asthma control, and symptoms. Thus, the use of blood eosinophils as a baseline biomarker could help to select patients with severe uncontrolled asthma who are likely to achieve benefits in asthma control with reslizumab. In conclusion, targeted therapy with reslizumab represents one step closer to precision medicine in patients with severe eosinophilic asthma.

摘要

人类嗜酸性粒细胞约占外周血白细胞的1%。然而,这些细胞有离开血流并迁移至炎症组织的倾向。嗜酸性粒细胞炎症在相当比例的重度哮喘患者中存在。哮喘是一种慢性炎症性疾病,全球有超过3.15亿人受其影响,其中10%患有严重的未得到控制的疾病。尽管大多数患者能够得到有效治疗,但重度哮喘患者仍未得到控制,有病情加重甚至死亡的风险。白细胞介素-5(IL-5)在嗜酸性粒细胞的分化、成熟、激活及抑制凋亡过程中发挥着重要作用。因此,靶向IL-5是治疗重度嗜酸性粒细胞性哮喘患者的一种有吸引力的方法。瑞利珠单抗是一种人源化抗IL-5单克隆抗体,与对结合IL-5受体α至关重要的IL-5的89-92位氨基酸具有高亲和力。两项III期研究表明,在患有重度哮喘和嗜酸性粒细胞增多(≥400个细胞/μL)的成年患者中使用瑞利珠单抗可改善肺功能、哮喘控制情况及症状。因此,将血液嗜酸性粒细胞作为基线生物标志物有助于选择可能从使用瑞利珠单抗控制哮喘中获益的重度未控制哮喘患者。总之,瑞利珠单抗的靶向治疗使重度嗜酸性粒细胞性哮喘患者向精准医学迈进了一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b90/5344894/e0a65eb3f859/fimmu-08-00242-g001.jpg

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