Human GM-CSF Autoantibodies and Reproduction of Pulmonary Alveolar Proteinosis

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Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF act...

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Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis.

BACKGROUND Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. METHODS Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveo...

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Pulmonary alveolar proteinosis is a rare condition traditionally requiring treatment with whole lung lavage. The case is presented of a young man who obtained complete remission following treatment with granulocyte-macrophage colony stimulating factor, a new treatment option.

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Pulmonary epithelial cell expression of GM-CSF corrects the alveolar proteinosis in GM-CSF-deficient mice.

Mutation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by homologous recombination caused alveolar proteinosis in mice. To further discern the role of GM-CSF in surfactant homeostasis, the synthesis of GM-CSF was directed to the respiratory epithelium of GM-CSF-hull mutant mice (GM-/-) with a chimeric gene expressing GM-CSF under the control of the promoter from the huma...

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Pulmonary alveolar proteinosis (PAP) is a rare disorder of unknown origin characterized by alveolar fillings with periodic acid-Schiff (PAS)-positive material mainly consisting of phospholipids. Mice defective in the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene or the GM-CSF/interleukin (IL)-3/IL-5-receptor common beta chain (beta c) demonstrate a pathology resembling PAP. A r...

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ژورنال

عنوان ژورنال: New England Journal of Medicine

سال: 2009

ISSN: 0028-4793,1533-4406

DOI: 10.1056/nejmc0904077