Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis
| Autor: | Bashir, Alexandra Kristin, Wink, Lisa, Duller, Stefanie, Schwendner, Petra, Cockell, Charles, Rettberg, Petra, Mahnert, Alexander, Beblo-Vranesevic, Kristina, Bohmeier, Maria, Rabbow, Elke, Gaboyer, Frederic, Westall, Frances, Walter, Nicolas, Cabezas, Patricia, Garcia-Descalzo, Laura, Gomez, Felipe, Malki, Mustapha, Amils, Ricardo, Ehrenfreund, Pascale, Monaghan, Euan, Vannier, Pauline, Marteinsson, Viggo, Erlacher, Armin, Tanski, George, Strauss, Jens, Bashir, Mina, Riedo, Andreas, Moissl-Eichinger, Christine |
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| Přispěvatelé: | Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), UK Centre for Astrobiology, SUPA School of Physics and Astronomy [Edinburgh], University of Edinburgh-University of Edinburgh, University of Edinburgh, DLR Institut für Luft- und Raumfahrtmedizin, Deutsches Zentrum für Luft- und Raumfahrt [Köln] (DLR), Medical University Graz, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Multiple Organ Failure Inflammation Methionine-tRNA Ligase Pulmonary Alveolar Proteinosis Systemic inflammation Bronchoalveolar Lavage 03 medical and health sciences Liver disease chemistry.chemical_compound Methionine 0302 clinical medicine Internal medicine Extracellular Humans Medicine 030212 general & internal medicine Respiratory system Child chemistry.chemical_classification Reactive oxygen species business.industry medicine.disease 3. Good health Endocrinology 030228 respiratory system chemistry Child Preschool Dietary Supplements [SDV.IMM]Life Sciences [q-bio]/Immunology medicine.symptom Reactive Oxygen Species business Pulmonary alveolar proteinosis |
| Zdroj: | European Respiratory Journal European Respiratory Journal, European Respiratory Society, 2021, pp.2101554. ⟨10.1183/13993003.01554-2021⟩ |
| ISSN: | 0903-1936 1399-3003 |
| Popis: | IntroductionPulmonary 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.MethodsFour 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 production by patient monocytes before and after methionine supplementation was also studied.ResultsMethionine 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 noninvasive ventilation could be weaned off within 60 days. In addition, liver dysfunction, inflammation and growth delay improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes.ConclusionMethionine 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. |
| Databáze: | OpenAIRE |
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