Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-01-01 DOI:10.1016/j.alit.2023.06.001
Hitoshi Sasano , Norihiro Harada , Sonoko Harada , Tomohito Takeshige , Yuuki Sandhu , Yuki Tanabe , Ayako Ishimori , Kei Matsuno , Tetsutaro Nagaoka , Jun Ito , Asako Chiba , Hisaya Akiba , Ryo Atsuta , Kenji Izuhara , Sachiko Miyake , Kazuhisa Takahashi
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引用次数: 1

Abstract

Background

Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical responsiveness to mepolizumab after 1-year treatment.

Methods

Twenty-seven patients with severe asthma were treated with mepolizumab for one year. Asthma control test scores, pulmonary function tests, fractional exhaled nitric oxide levels, and blood samples were evaluated. Additionally, we explored the role of CD69-positive mucosal-associated invariant T (MAIT) cells as a candidate biomarker for predicting treatment effectiveness by evaluating an OVA-induced asthma murine model using MR1 knockout mice, where MAIT cells were absent.

Results

The frequencies of CD69-positive group 1 innate lymphoid cells, group 3 innate lymphoid cells, natural killer cells, and MAIT cells decreased after mepolizumab treatment. The frequency of CD69-positive MAIT cells and neutrophils was lower and serum periostin levels were higher in responders than in non-responders. In the OVA-induced asthma murine model, CD69-positive MAIT cell count in the whole mouse lung was significantly higher than that in the control mice. Moreover, OVA-induced eosinophilic airway inflammation was exacerbated in the MAIT cell-deficient MR1 knockout mice.

Conclusions

This study shows that circulating CD69-positive MAIT cells, neutrophils, and serum periostin might predict the real-world response after 1-year mepolizumab treatment. Furthermore, MAIT cells potentially have a protective role against type 2 airway inflammation.

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治疗前循环 MAIT 细胞、中性粒细胞和包膜蛋白可预测哮喘患者接受 1 年美泊珠单抗治疗后的实际反应
背景美妥珠单抗治疗可改善严重嗜酸性粒细胞性哮喘患者的症状控制和生活质量,并减少病情恶化。然而,必须确定预测疗效的生物标志物,以便用于精准医疗。在此,我们阐明了治疗前后各种参数的动态变化,以及治疗一年后预测对美泊珠单抗临床反应性的患者特征。我们对哮喘控制测试评分、肺功能测试、呼出一氧化氮分数水平和血液样本进行了评估。此外,我们还通过评估 OVA 诱导的哮喘小鼠模型,使用 MR1 基因敲除小鼠(MR1 基因敲除小鼠不存在 MAIT 细胞),探讨了 CD69 阳性粘膜相关不变 T 细胞(MAIT)作为预测治疗效果的候选生物标记物的作用。与非应答者相比,应答者 CD69 阳性 MAIT 细胞和中性粒细胞的频率较低,血清包膜生长因子水平较高。在 OVA 诱导的哮喘小鼠模型中,小鼠全肺中 CD69 阳性 MAIT 细胞数明显高于对照组小鼠。此外,在 MAIT 细胞缺陷的 MR1 基因敲除小鼠中,OVA 诱导的嗜酸性粒细胞气道炎症会加重。结论这项研究表明,循环中 CD69 阳性的 MAIT 细胞、中性粒细胞和血清包膜生长因子可能会预测美妥珠单抗治疗 1 年后的真实世界反应。此外,MAIT 细胞可能对 2 型气道炎症具有保护作用。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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