Out of breath: GM-CSFRalpha mutations disrupt surfactant homeostasis.
Pulmonary alveolar proteinosis (PAP) is a rare disorder in which surfactant homeostasis in the lung is impaired, causing respiratory distress and, in severe cases, respiratory failure. Most cases of PAP are associated with the formation of autoantibodies against the cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF), which is required for normal surfactant homeostasis and lung function. New studies now identify three patients in whom PAP was caused by mutations in the gene encoding the ligand-binding alpha chain of the GM-CSF receptor.
Notarangelo
Luigi D
LD
Division of Immunology, The Manton Center for Orphan Disease Research, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA. luigi.notarangelo@childrens.harvard.edu
Pessach
Itai
I
D000818:Animals; D041321:Chromosomes, Human, X / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics / Q000503:physiopathology; D011663:Pulmonary Surfactants / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C521678:CSF2RA protein, human; D021122:Protein Subunits; D011663:Pulmonary Surfactants; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor