This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonfield, T. L. Articles by Thomassen, M. J. Search for Related Content PubMed PubMed Citation Articles by Bonfield, T. L. Articles by Thomassen, M. J.

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

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

This article has been cited by other articles:

				T. L. Bonfield, M. J. Thomassen, C. F. Farver, S. Abraham, M. T. Koloze, X. Zhang, D. M. Mosser, and D. A. Culver Peroxisome Proliferator-Activated Receptor-{gamma} Regulates the Expression of Alveolar Macrophage Macrophage Colony-Stimulating Factor J. Immunol., July 1, 2008; 181(1): 235 - 242. [Abstract] [Full Text] [PDF]

				A. A. Frazier, T. J. Franks, E. O. Cooke, T.-L. H. Mohammed, R. D. Pugatch, and J. R. Galvin From the Archives of the AFIP: Pulmonary Alveolar Proteinosis RadioGraphics, May 1, 2008; 28(3): 883 - 899. [Abstract] [Full Text] [PDF]

				O C Ioachimescu and M S Kavuru Pulmonary alveolar proteinosis Chronic Respiratory Disease, July 1, 2006; 3(3): 149 - 159. [Abstract] [PDF]

				S. B. Venkateshiah, T. D. Yan, T. L. Bonfield, M. J. Thomassen, M. Meziane, C. Czich, and M. S. Kavuru An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis. Chest, July 1, 2006; 130(1): 227 - 237. [Abstract] [Full Text] [PDF]

				F-C Lin, G-D Chang, M-S Chern, Y-C Chen, and S-C Chang Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis Thorax, June 1, 2006; 61(6): 528 - 534. [Abstract] [Full Text] [PDF]

				M. E. Wylam, R. Ten, U. B. S. Prakash, H. F. Nadrous, M. L. Clawson, and P. M. Anderson Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis. Eur. Respir. J., March 1, 2006; 27(3): 585 - 593. [Abstract] [Full Text] [PDF]

				T. L. Bonfield, C. M. Swaisgood, B. P. Barna, C. F. Farver, M. S. Kavuru, and M. J. Thomassen Elevated gelatinase activity in pulmonary alveolar proteinosis: role of macrophage-colony stimulating factor J. Leukoc. Biol., January 1, 2006; 79(1): 133 - 139. [Abstract] [Full Text] [PDF]

				T. L. Bonfield, N. John, B. P. Barna, M. S. Kavuru, M. J. Thomassen, and B. Yen-Lieberman Multiplexed Particle-Based Anti-Granulocyte Macrophage Colony Stimulating Factor Assay Used as Pulmonary Diagnostic Test Clin. Vaccine Immunol., July 1, 2005; 12(7): 821 - 824. [Abstract] [Full Text] [PDF]

				P Latzin, M Tredano, Y Wust, J de Blic, T Nicolai, B Bewig, F Stanzel, D Kohler, M Bahuau, and M Griese Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis Thorax, January 1, 2005; 60(1): 39 - 44. [Abstract] [Full Text] [PDF]

				S. Meaney, T. L. Bonfield, M. Hansson, A. Babiker, M. S. Kavuru, and M. J. Thomassen Serum cholestenoic acid as a potential marker of pulmonary cholesterol homeostasis: increased levels in patients with pulmonary alveolar proteinosis J. Lipid Res., December 1, 2004; 45(12): 2354 - 2360. [Abstract] [Full Text] [PDF]

				A. Bush Paediatric interstitial lung disease: not just kid's stuff Eur. Respir. J., October 1, 2004; 24(4): 521 - 523. [Full Text] [PDF]

				F. Brasch, J. Birzele, M. Ochs, S.H. Guttentag, O.D. Schoch, A. Boehler, M.F. Beers, K.M. Muller, S. Hawgood, and G. Johnen Surfactant proteins in pulmonary alveolar proteinosis in adults Eur. Respir. J., September 1, 2004; 24(3): 426 - 435. [Abstract] [Full Text] [PDF]

				G. L. Snider Only Cell and Molecular Biology Can Lead to an Understanding of Pathogenesis of Lung Disease Am. J. Respir. Crit. Care Med., July 1, 2004; 170(1): i - ii. [Full Text]

				A. Perez IV and R. M. Rogers Enhanced Alveolar Clearance With Chest Percussion Therapy and Positional Changes During Whole-Lung Lavage for Alveolar Proteinosis Chest, June 1, 2004; 125(6): 2351 - 2356. [Abstract] [Full Text] [PDF]

				M. Beccaria, M. Luisetti, G. Rodi, A. Corsico, M.C. Zoia, S. Colato, P. Pochetti, A. Braschi, E. Pozzi, and I. Cerveri Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis Eur. Respir. J., April 1, 2004; 23(4): 526 - 531. [Abstract] [Full Text] [PDF]

				K. Uchida, K. Nakata, B. C. Trapnell, T. Terakawa, E. Hamano, A. Mikami, I. Matsushita, J. F. Seymour, M. Oh-eda, I. Ishige, et al. High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis Blood, February 1, 2004; 103(3): 1089 - 1098. [Abstract] [Full Text] [PDF]

				B. C. Trapnell, J. A. Whitsett, and K. Nakata Pulmonary Alveolar Proteinosis N. Engl. J. Med., December 25, 2003; 349(26): 2527 - 2539. [Full Text] [PDF]

				T. L. Bonfield, C. F. Farver, B. P. Barna, A. Malur, S. Abraham, B. Raychaudhuri, M. S. Kavuru, and M. J. Thomassen Peroxisome Proliferator-Activated Receptor-{gamma} Is Deficient in Alveolar Macrophages from Patients with Alveolar Proteinosis Am. J. Respir. Cell Mol. Biol., December 1, 2003; 29(6): 677 - 682. [Abstract] [Full Text] [PDF]

				T. L. Bonfield, B. Raychaudhuri, A. Malur, S. Abraham, B. C. Trapnell, M. S. Kavuru, and M. J. Thomassen PU.1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage colony-stimulating factor Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1132 - L1136. [Abstract] [Full Text] [PDF]