Exploring Inflammatory and Regulatory Eosinophil Subpopulations: the Path to Precision Medicine for the Treatment of Eosinophilic-associated Diseases
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 160
- 主要终点
- Primary objective: first outcome measure
研究概览
简要总结
This single-center, non-commercial study will involve 160 participants (80 with eosinophilic asthma (EA), 30 with eosinophilic granulomatosis with polyangiitis (EGPA), 25 with hypereosinophilic syndrome (HES), and 25 healthy donors) to investigate eosinophil subpopulations in these diseases. The study will run from Q4 2024 to Q4 2026.
Objectives:
Primary: To verify two eosinophil subpopulations (iEos and rEos) in EGPA and HES and analyze the role of type 2 cytokines on their plasticity.
Secondary: Compare iEos proportion between different eosinophilic diseases and correlate with disease severity.
Exploratory: Assess the effect of mepolizumab on eosinophil subpopulations in vitro.
Population: Adults aged 18-75 with EA, EGPA, or HES, and healthy controls. EA patients must have >300 eosinophils/mcL, EGPA requires asthma + eosinophilia + other specific features, and HES requires high eosinophil counts (>1500 cells/mL).
Methods: Data will be analyzed using Mann-Whitney U, ANOVA, and Spearman correlation tests, with results presented as mean ± SEM.
This study will help explore eosinophil behavior in eosinophilic diseases and evaluate mepolizumab's effects on these cells.
详细描述
Introduction Eosinophils (Eos) play a crucial role in both normal physiological functions and various pathological conditions. They are primarily recognized for their involvement in immune defense against infections, including parasitic, bacterial, and viral infections, as well as in cancer surveillance. However, they are also key contributors to eosinophil-associated diseases (EADs) such as bronchial asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and hypereosinophilic syndrome (HES).
Recent research has revealed that eosinophils exist in distinct subpopulations with unique phenotypic characteristics and functions. These subpopulations, referred to as resident eosinophils (rEos) and inflammatory eosinophils (iEos), have been primarily studied in healthy tissues and in conditions like severe eosinophilic asthma (SEA) and CRSwNP. While rEos are believed to contribute to tissue homeostasis and immune regulation, iEos are associated with inflammatory responses. Studies in mouse models have demonstrated the presence of these subpopulations in lung tissue, but their role in human disease remains less understood.
Although there is emerging evidence suggesting the presence of these eosinophil subsets in human peripheral blood and nasal polyp tissue, they have not been fully characterized in other EADs such as EGPA and HES. Understanding whether these subpopulations exist in these diseases and how they are influenced by type 2 cytokines could provide valuable insights into disease mechanisms. Furthermore, as eosinophil-targeted therapies such as Mepolizumab (an anti-IL-5 monoclonal antibody) are already in clinical use, clarifying their specific effects on these eosinophil subsets could help optimize treatment strategies.
Study Rationale and Objectives This study aims to expand on previous findings by investigating whether distinct eosinophil subpopulations exist in EGPA and HES patients. Additionally, the study seeks to analyze how type 2 cytokines influence the differentiation and function of these eosinophil subsets. A key aspect of this research is assessing the effect of Mepolizumab on rEos and iEos, particularly whether it selectively targets inflammatory eosinophils without affecting homeostatic eosinophils.
The primary objectives of this study include:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For inclusion in the study subjects should fulfill the following criteria based on local regulations:
- •Patients with Asthma, or EGPA or HES:
- •Age between 18 and 75 years at the time of signing the informed consent
- •Patients with EA, EGPA or HES
- •Provision of signed and dated written informed consent form prior to any mandatory study procedures, sampling and analysis.
- •Healthy donors:
- •Age between18 and 75 years healthy donors
排除标准
- •Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
- •Presence of other chronic pulmonary diseases including COPD
- •Presence of other chronic immuno-mediated inflammatory diseases
- •Treatment with oral prednisone or equivalent > 7.5 mg/day
- •Treatment with long-acting depot corticosteroids in the last three months
- •Use of immunosuppressive medications (cyclosporine A; azathioprine; methotrexate; mycophenolate mofetil)
- •Receipt of live attenuated vaccines 30 days prior to the enrollment
- •Acute upper or lower respiratory infections within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
- •A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy
- •Subjects who are pregnant or breastfeeding
- •Current smoking
- •Any clinically significant abnormal findings in physical examination, vital signs, hematology, or clinical chemistry during screening period, which in the opinion of the investigator may put the patient at risk of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study.
- •Concurrent enrolment in another interventional or post-authorization safety study.
结局指标
主要结局
Primary objective: first outcome measure
时间窗: From the enrollment of the first patient at 20 months
1) Proportion of circulating Siglec8+CD16-CD62Llow (iEos) and Siglec8+CD16-CD62Lbright (rEos) cells in bio- naïve, EGPA and HES patients
Primary objective: second outcome measure
时间窗: From the enrollment of the first patient at 20 months
2) Modification of the expression of CD62L on peripheral eosinophils upon in vitro stimulation with IL-5, IL-3, GM-CSF, IL-4, IL-13
次要结局
- Secondary objective: first outcome measure(From the enrollment of the first patient at 18 months)
- Secondary objective: second outcome measure(From the enrollment of the first patient at 18 months)
研究者
Alessandra Vultaggio
Principal investigator, researcher
University of Florence