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NCT Number: NCT04811274

Macrophages, GM-CSF and MARS Proteinosis

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).

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Key information

Conditions

Pulmonary Alveolar Proteinosis (PAP) Genetic Mutation Lung Diseases MARS Pulmonary Alveolar Proteinosis Respiratory Tract Diseases

Age range

Up to 17 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital Necker-Enfants Malades

Paris, 75015, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Blood collection

Biological

2 to 5 ml

Bronchoalveolar lavage fluid collection

Biological

5 to 25 ml

Primary outcomes

  1. Measurement of the clearance

    Time frame: 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.

Secondary outcomes

  1. Measurement of the clearance after supplementation with methionine

    Time frame: Day 0

    Measurement of the clearance of abnormal lipo-proteinaceous material (from patients) at 48h culture with methionine supplementation in culture medium 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.

  2. Cellular phenotyping and study of the GM-CSF pathway

    Time frame: Day 0

    Description : Study the impact of mutations on the cell phenotype and the GM-CSF signalling pathway.

    (i) CD11b and CD49d cell immunostaining which are surface markers of healthy alveolar macrophages ; (ii) measurement of the level of intracellular phosphorylation of STAT5 by flow cytometry; and (iii) measurement of the level of expression of the SPI1, PPARγ and ABCG1 genes by quantitative PCR.

    These measurements will be performed in cultured macrophages derived from peripheral blood monocytes of patients and controls, but also in alveolar macrophages directly isolated from the BAL fluid of patients and controls. All these measurements will be performed in response to incubation with GM-CSF.

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • URC-CIC Paris Descartes Necker Cochin

Registry information

Official study title

Study of Macrophage Function and of the GM-CSF Signaling Pathway in Alveolar Proteinosis by Mutations of the MARS Gene

Acronym: MacroMARS

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Mar 23, 2021
Registry last updated
Apr 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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