Study of Macrophage Function and of the GM-CSF Signaling Pathway in Alveolar Proteinosis by Mutations of the MARS Gene
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Measurement of the clearance
研究概览
简要总结
Mutations in the MARS gene encoding methionyl-tRNA synthetase are responsible for a genetic form of alveolar proteinosis (PAP), but the pathophysiological mechanisms of the respiratory phenotype are not known.
The main hypothesis is that the PAP phenotype in these patients is secondary to a defective clearance of the surfactant by the alveolar macrophages.
The main objective of the study is to study the clearance capacity of lipoproteinaceous material by macrophages of patients with MARS related PAP. This will be investigate in cultured macrophages derived from peripheral blood monocytes of patients (patients with MARS related PAP) and controls (patients without MARS related PAP).
详细描述
Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease characterized by the accumulation of lipoproteinaceous material within the pulmonary alveoli, resulting in the majority of cases from a defective clearance of the surfactant by intra-alveolar macrophages.
Mutations in the MARS gene encoding methionyl-tRNA synthetase are responsible for a genetic form of alveolar proteinosis, but the pathophysiological mechanisms leading to mutations in the respiratory phenotype are not known.
The main hypothesis is that the alveolar proteinosis phenotype in these patients is secondary to a defective clearance of the surfactant by the alveolar macrophages.
The main objective of the study is to study the clearance capacity of lipoproteinaceous material by macrophages of patients with MARS related PAP. This will be investigate in cultured macrophages derived from peripheral blood monocytes of patients (patients with MARS related PAP) and controls (patients without MARS related PAP).
The subjects and the controls will be included during a hospitalization during which a blood sample and a bronchoscopy with broncoalveolar lavage must be performed as part of their care.
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Minors from 0 to 17 years hospitalized for their care at Necker Enfants Malades hospital and for whom a blood sample and a bronchoscopy with bronchoalveolar lavage must be performed as part of their care
- •Information and consent of the holders of parental authority and the patient
排除标准
- •- Refusal of holders of parental authority or patient
研究组 & 干预措施
Patients
Minor patients with alveolar proteinosis by mutations of the MARS gene.
干预措施: Blood collection (Biological)
Patients
Minor patients with alveolar proteinosis by mutations of the MARS gene.
干预措施: Bronchoalveolar lavage fluid collection (Biological)
Controls
Minors patients without alveolar proteinosis.
干预措施: Blood collection (Biological)
Controls
Minors patients without alveolar proteinosis.
干预措施: Bronchoalveolar lavage fluid collection (Biological)
结局指标
主要结局
Measurement of the clearance
时间窗: Day 0
Measurement of the clearance of abnormal lipo-proteinaceous material (from patients) at 48h of culture by cultured macrophages derived from peripheral blood monocytes from patients and controls. Microscopic examination of cell samples prepared on slide after cytospin and stained with oil red'O.
次要结局
- Measurement of the clearance after supplementation with methionine(Day 0)
- Cellular phenotyping and study of the GM-CSF pathway(Day 0)