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American Journal of Respiratory Cell and Molecular Biology. Vol. 27, pp. 481-486, 2002
© 2002 American Thoracic Society
DOI: 10.1165/rcmb.2002-0023OC

Autoantibodies against Granulocyte Macrophage Colony–Stimulating Factor Are Diagnostic for Pulmonary Alveolar Proteinosis

Tracey L. Bonfield, Debra Russell, Sujata Burgess, Anagha Malur, Mani S. Kavuru and Mary Jane Thomassen

Departments of Pulmonary and Critical Care Medicine and Cell Biology, The Cleveland Clinic Foundation, Cleveland, Ohio

Address correspondence to: Dr. Mary Jane Thomassen, Department of Pulmonary and Critical Care Medicine, 9500 Euclid Avenue, Cleveland Clinic Foundation, Desk A90, Cleveland, OH 44195-5038. E-mail: thomasm{at}ccf.org

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of phospholipids and surfactant proteins in the lung. The central role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in surfactant homeostasis has been established in mice lacking the GM-CSF gene, which results in murine pulmonary alveolar proteinosis. No GM-CSF gene defect has been defined in adult patients with idiopathic PAP. Previous studies indicated that the human disease differs from the murine model by the presence of circulating, neutralizing autoantibodies against GM-CSF. Therefore, the final common pathway between the GM-CSF knockout and human PAP appears to be the deficiency of functionally active GM-CSF. In the present study, all patients with idiopathic PAP were found to have systemic and localized antibodies against GM-CSF. Anti–GM-CSF titers were a specific and sensitive marker for PAP. In addition, we present data showing that the absence of active GM-CSF is associated with enhanced levels of macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and interleukin-8. These studies confirm and strengthen previous studies and support the concept that adult idiopathic PAP is an autoimmune disease defined by the presence of anti–GM-CSF. Further, using anti–GM-CSF as an indicator of pulmonary alveolar proteinosis may avoid the use of more invasive means of evaluating patients with pulmonary disease characterized by alveolar infiltrates.

Abbreviations: bronchoalveolar lavage, BAL • enzyme-linked immunosorbent assay, ELISA • granulocyte-macrophage colony-stimulating factor, GM-CSF • interleukin, IL • monocytes chemotactic protein, MCP • macrophage colony-stimulating factor, M-CSF • pulmonary alveolar proteinosis, PAP • tris-buffered saline, TBS




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