Roles of the autoantibody against GM-CSF in the pathogenesis, diagnosis, and treatment for idiopathic pulmonary alveolar proteinosis

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Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome with currently three recognised forms ; congenital, secondary and acquired. More than 90% of cases are of the latter type, which recently has been characterized as an acquired autoimmune disorder. In PAP excess accumulation of surfactant leads to characteristic bilateral airspace opacities on chest radiograph and extensive alveolar densities with thickened interlobular septa on computed tomography scan. PAP typically appears in previously healthy individuals, who present with several months of dyspnoea and impaired pulmonary gas transfer of variable severity. "Milky" appearing, lipid-rich fluid recovered at bronchoalveolar lavage is characteristic, while lung biopsy, when performed, shows minimally inflamed alveoli uniformly filled with amorphous eosinophilic material that on electron microscopy contains characteristic lamellar bodies. Current concepts of pathogenesis in acquired PAP are that the excess surfactant results from impaired clearance by alveolar macrophages, as a result of inhibition by specific polyclonal autoantibodies of trophic physiological signals from the endogenous cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). Current therapy consists of whole-lung lavage under general anesthesia, repeated as needed by clinical status, while some adult patients also respond to the repeated administration of recombinant human GM-CSF.