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Article Dans Une Revue European Respiratory Journal Année : 2021

Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis

Alice Hadchouel
David Drummond
Clément Pontoizeau
Laura Aoust
  • Fonction : Auteur
Jamel El-Benna
Elsa Gachelin
  • Fonction : Auteur
Caroline Perisson
  • Fonction : Auteur
Clémentine Vigier
  • Fonction : Auteur
Florence Lacaille
Sylvain Renolleau
  • Fonction : Auteur
Chris Ottolenghi
Jean-Marc Tréluyer
  • Fonction : Auteur
Jacques de Blic
  • Fonction : Auteur
Christophe Delacourt

Résumé

Introduction Pulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase ( MARS1 ) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease. Methods Four patients received methionine supplementation and were followed for respiratory, hepatic, growth, and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species (ROS) production by patient monocytes before and after methionine supplementation was also studied. Results Methionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material, and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or non-invasive ventilation could be weaned off within 60 days. Liver dysfunction, inflammation, and growth delay also improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes. Conclusion Methionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the MARS1 gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.

Domaines

Immunologie
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Dates et versions

hal-03447784 , version 1 (24-11-2021)

Identifiants

Citer

Alice Hadchouel, David Drummond, Clément Pontoizeau, Laura Aoust, Maria-Margarita Hurtado Nedelec, et al.. Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis. European Respiratory Journal, 2021, pp.2101554. ⟨10.1183/13993003.01554-2021⟩. ⟨hal-03447784⟩

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