Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis.

Idiopathic pulmonary alveolar proteinosis is a rare disease in which surfactant lipids and proteins accumulate in pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and, in severe cases, respiratory failure. Granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibodies occur in these patients and may mediate the pathogenesis of this disease, but they are also present in healthy persons and in immune globulin prepared from plasma obtained from healthy persons. Since GM-CSF is required for surfactant catabolism by alveolar macrophages in mice, we hypothesized that high levels of GM-CSF autoantibodies (i.e., levels sufficient to eliminate endogenous GM-CSF priming of myeloid cells) could cause idiopathic pulmonary alveolar proteinosis by impairing surfactant clearance by alveolar macrophages. We previously found that high levels of GM-CSF autoantibodies are specifically associated with idiopathic pulmonary alveolar proteinosis and can be isolated in pure form from these patients