Clinical trial NCT04811274: Macrophages, GM-CSF and MARS Proteinosis
Official title: Study of Macrophage Function and of the GM-CSF Signaling Pathway in Alveolar Proteinosis by Mutations of the MARS Gene
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Alveolar Proteinosis (PAP)
MARS
Genetic Mutation
Keywords: Pulmonary alveolar proteinosis (PAP)
Mutations in the MARS gene
Methionyl-tRNA synthetase
Surfactant clearance
Alveolar macrophages
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-03-23
Enrollment: 20
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Minor patients with alveolar proteinosis by mutations of the MARS gene and minor patients without alveolar proteinosis, hospitalized for their care at Necker Enfants Malades hospital and for whom a blood sample and a bronchoscopy with bronchoalveolar lavage must be performed for their care.

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

- Refusal of holders of parental authority or patient

Primary outcomes:
measure: Measurement of the clearance
timeFrame: Day 0
Secondary outcomes:
measure: Measurement of the clearance after supplementation with methionine
timeFrame: Day 0
measure: Cellular phenotyping and study of the GM-CSF pathway
timeFrame: Day 0
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Alice HADCHOUEL
role: PRINCIPAL_INVESTIGATOR
References: