Idiopathic Pulmonary Alveolar Proteinosis as an Autoimmune Disease with Neutralizing Antibody against Granulocyte/Macrophage Colony-Stimulating Factor

doi:10.1084/jem.190.6.875

This Article

	Full Text
	Full Text (PDF, 142K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Kitamura, T.
	Articles by Nakata, K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Kitamura, T.
	Articles by Nakata, K.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/1999/9/875/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 875-880

Idiopathic Pulmonary Alveolar Proteinosis as an Autoimmune Disease with Neutralizing Antibody against Granulocyte/Macrophage Colony-Stimulating Factor

Takayuki Kitamura^a, Naohiko Tanaka^a,b, Junichi Watanabe^a, Kanji Uchida^a, Shiro Kanegasaki^a, Yoshitsugu Yamada^a, and Koh Nakata
^a The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
^b Kitasato University School of Medicine, Kanagawa 228-8655, Japan

Correspondence to: Koh Nakata, Laboratory of Culture Collection, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan. Tel:81-3-5449-5391 Fax:81-3-5449-5254 E-mail:kinkabu{at}hgc.ims.u-tokyo.ac.jp.

Idiopathic pulmonary alveolar proteinosis (I-PAP) is a raredisease of unknown etiology in which the alveoli fill with lipoproteinaceousmaterial. We report here that I-PAP is an autoimmune diseasewith neutralizing antibody of immunoglobulin G isotype againstgranulocyte/macrophage colony-stimulating factor (GM-CSF). Theantibody was found to be present in all specimens of bronchoalveolarlavage fluid obtained from 11 I-PAP patients but not in samplesfrom 2 secondary PAP patients, 53 normal subjects, and 14 patientswith other lung diseases. It specifically bound GM-CSF and neutralizedbioactivity of the cytokine in vitro. The antibody was alsofound in sera from all I-PAP patients examined but not in serafrom a secondary PAP patient or normal subjects, indicatingthat it exists systemically in I-PAP patients. As lack of GM-CSFsignaling causes PAP in congenital cases and PAP-like diseasein murine models, our findings strongly suggest that neutralizationof GM-CSF bioactivity by the antibody causes dysfunction ofalveolar macrophages, which results in reduced surfactant clearance.

Key Words: autoantibody, granulocyte/macrophage colony-stimulating factor,pulmonary alveolar proteinosis, alveolar macrophage, surfactantprotein

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Martinez-Moczygemba, M., Doan, M. L., Elidemir, O., Fan, L. L., Cheung, S. W., Lei, J. T., Moore, J. P., Tavana, G., Lewis, L. R., Zhu, Y., Muzny, D. M., Gibbs, R. A., Huston, D. P. (2008). Pulmonary alveolar proteinosis caused by deletion of the GM-CSFR{alpha} gene in the X chromosome pseudoautosomal region 1. JEM 205: 2711-2716 [Abstract] [Full Text]
Suzuki, T., Sakagami, T., Rubin, B. K., Nogee, L. M., Wood, R. E., Zimmerman, S. L., Smolarek, T., Dishop, M. K., Wert, S. E., Whitsett, J. A., Grabowski, G., Carey, B. C., Stevens, C., van der Loo, J. C.M., Trapnell, B. C. (2008). Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. JEM 205: 2703-2710 [Abstract] [Full Text]
Notarangelo, L. D., Pessach, I. (2008). Out of breath: GM-CSFR{alpha} mutations disrupt surfactant homeostasis. JEM 205: 2693-2697 [Abstract] [Full Text]
Woischnik, M., Bauer, A., Aboutaam, R., Pamir, A., Stanzel, F., de Blic, J., Griese, M. (2008). Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis. Eur Respir J 31: 1197-1204 [Abstract] [Full Text]
Inoue, Y., Trapnell, B. C., Tazawa, R., Arai, T., Takada, T., Hizawa, N., Kasahara, Y., Tatsumi, K., Hojo, M., Ichiwata, T., Tanaka, N., Yamaguchi, E., Eda, R., Oishi, K., Tsuchihashi, Y., Kaneko, C., Nukiwa, T., Sakatani, M., Krischer, J. P., Nakata, K., for the Japanese Center of the Rare Lung Diseases, (2008). Characteristics of a Large Cohort of Patients with Autoimmune Pulmonary Alveolar Proteinosis in Japan. Am. J. Respir. Crit. Care Med. 177: 752-762 [Abstract] [Full Text]
Wojcik, A. J., Skaflen, M. D., Srinivasan, S., Hedrick, C. C. (2008). A Critical Role for ABCG1 in Macrophage Inflammation and Lung Homeostasis. J. Immunol. 180: 4273-4282 [Abstract] [Full Text]
Thomassen, M. J., Barna, B. P., Malur, A. G., Bonfield, T. L., Farver, C. F., Malur, A., Dalrymple, H., Kavuru, M. S., Febbraio, M. (2007). ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis. J. Lipid Res. 48: 2762-2768 [Abstract] [Full Text]
Uchida, K., Beck, D. C., Yamamoto, T., Berclaz, P.-Y., Abe, S., Staudt, M. K., Carey, B. C., Filippi, M.-D., Wert, S. E., Denson, L. A., Puchalski, J. T., Hauck, D. M., Trapnell, B. C. (2007). GM-CSF Autoantibodies and Neutrophil Dysfunction in Pulmonary Alveolar Proteinosis. NEJM 356: 567-579 [Abstract] [Full Text]
Dexter, M. E., Cosgrove, G. P., Douglas, I. S. (2007). Managing a Rare Condition Presenting With Intractable Hypoxemic Respiratory Failure. Chest 131: 320-327 [Full Text]
Ioachimescu, O C, Kavuru, M S (2006). Pulmonary alveolar proteinosis. Chronic Respiratory Disease 3: 149-159 [Abstract]
Venkateshiah, S. B., Yan, T. D., Bonfield, T. L., Thomassen, M. J., Meziane, M., Czich, C., Kavuru, M. S. (2006). An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis.. Chest 130: 227-237 [Abstract] [Full Text]
Lin, F-C, Chang, G-D, Chern, M-S, Chen, Y-C, Chang, S-C (2006). Clinical significance of anti-GM-CSF antibodies in idiopathic pulmonary alveolar proteinosis. Thorax 61: 528-534 [Abstract] [Full Text]
Wylam, M. E., Ten, R., Prakash, U. B. S., Nadrous, H. F., Clawson, M. L., Anderson, P. M. (2006). Aerosol granulocyte-macrophage colony-stimulating factor for pulmonary alveolar proteinosis.. Eur Respir J 27: 585-593 [Abstract] [Full Text]
Bonfield, T. L., Swaisgood, C. M., Barna, B. P., Farver, C. F., Kavuru, M. S., Thomassen, M. J. (2006). Elevated gelatinase activity in pulmonary alveolar proteinosis: role of macrophage-colony stimulating factor. J. Leukoc. Biol. 79: 133-139 [Abstract] [Full Text]
Bonfield, T. L., John, N., Barna, B. P., Kavuru, M. S., Thomassen, M. J., Yen-Lieberman, B. (2005). Multiplexed Particle-Based Anti-Granulocyte Macrophage Colony Stimulating Factor Assay Used as Pulmonary Diagnostic Test. CVI 12: 821-824 [Abstract] [Full Text]
Tazawa, R., Hamano, E., Arai, T., Ohta, H., Ishimoto, O., Uchida, K., Watanabe, M., Saito, J., Takeshita, M., Hirabayashi, Y., Ishige, I., Eishi, Y., Hagiwara, K., Ebina, M., Inoue, Y., Nakata, K., Nukiwa, T. (2005). Granulocyte-Macrophage Colony-Stimulating Factor and Lung Immunity in Pulmonary Alveolar Proteinosis. Am. J. Respir. Crit. Care Med. 171: 1142-1149 [Abstract] [Full Text]
Bender, A. T., Ostenson, C. L., Wang, E. H., Beavo, J. A. (2005). Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation. Proc. Natl. Acad. Sci. USA 102: 497-502 [Abstract] [Full Text]
Latzin, P, Tredano, M, Wust, Y, de Blic, J, Nicolai, T, Bewig, B, Stanzel, F, Kohler, D, Bahuau, M, Griese, M (2005). Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis. Thorax 60: 39-44 [Abstract] [Full Text]
Bush, A. (2004). Paediatric interstitial lung disease: not just kid's stuff. Eur Respir J 24: 521-523 [Full Text]
Chiarini, R., Moran, O., Revoltella, R. P. (2004). Identification of an Antigenic Domain Near the C Terminus of Human Granulocyte-Macrophage Colony-stimulating Factor and Its Spatial Localization. J. Biol. Chem. 279: 37908-37917 [Abstract] [Full Text]
Brasch, F., Birzele, J., Ochs, M., Guttentag, S.H., Schoch, O.D., Boehler, A., Beers, M.F., Muller, K.M., Hawgood, S., Johnen, G. (2004). Surfactant proteins in pulmonary alveolar proteinosis in adults. Eur Respir J 24: 426-435 [Abstract] [Full Text]
Brasch, F., Griese, M., Tredano, M., Johnen, G., Ochs, M., Rieger, C., Mulugeta, S., Muller, K.M., Bahuau, M., Beers, M.F. (2004). Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene. Eur Respir J 24: 30-39 [Abstract] [Full Text]
Snider, G. L. (2004). Only Cell and Molecular Biology Can Lead to an Understanding of Pathogenesis of Lung Disease. Am. J. Respir. Crit. Care Med. 170: i-ii [Full Text]
Hellmich, B, Ciaglo, A, Schatz, H, Coakley, G (2004). Autoantibodies against granulocyte-macrophage colony stimulating factor and interleukin-3 are rare in patients with Felty's syndrome. Ann Rheum Dis 63: 862-866 [Abstract] [Full Text]
Morgan, C. (2004). The benefits of whole lung lavage in pulmonary alveolar proteinosis. Eur Respir J 23: 503-505 [Full Text]
Beccaria, M., Luisetti, M., Rodi, G., Corsico, A., Zoia, M.C., Colato, S., Pochetti, P., Braschi, A., Pozzi, E., Cerveri, I. (2004). Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. Eur Respir J 23: 526-531 [Abstract] [Full Text]
Uchida, K., Nakata, K., Trapnell, B. C., Terakawa, T., Hamano, E., Mikami, A., Matsushita, I., Seymour, J. F., Oh-eda, M., Ishige, I., Eishi, Y., Kitamura, T., Yamada, Y., Hanaoka, K., Keicho, N. (2004). High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Blood 103: 1089-1098 [Abstract] [Full Text]
Trapnell, B. C., Whitsett, J. A., Nakata, K. (2003). Pulmonary Alveolar Proteinosis. NEJM 349: 2527-2539 [Full Text]
Bonfield, T. L., Farver, C. F., Barna, B. P., Malur, A., Abraham, S., Raychaudhuri, B., Kavuru, M. S., Thomassen, M. J. (2003). Peroxisome Proliferator-Activated Receptor-{gamma} Is Deficient in Alveolar Macrophages from Patients with Alveolar Proteinosis. Am. J. Respir. Cell Mol. Bio. 29: 677-682 [Abstract] [Full Text]
Bonfield, T. L., Raychaudhuri, B., Malur, A., Abraham, S., Trapnell, B. C., Kavuru, M. S., Thomassen, M. J. (2003). PU.1 regulation of human alveolar macrophage differentiation requires granulocyte-macrophage colony-stimulating factor. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L1132-L1136 [Abstract] [Full Text]
Kavuru, M. S., Bonfield, T. L., Thomassen, M. J., Seymour, J. F., Presneill, J. J. (2003). Plasmapheresis, GM-CSF, and alveolar proteinosis. Am. J. Respir. Crit. Care Med. 167: 1036-1037 [Full Text]
Seymour, J F, Doyle, I R, Nakata, K, Presneill, J J, Schoch, O D, Hamano, E, Uchida, K, Fisher, R, Dunn, A R (2003). Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis. Thorax 58: 252-257 [Abstract] [Full Text]
Whitsett, J. A., Weaver, T. E. (2002). Hydrophobic Surfactant Proteins in Lung Function and Disease. NEJM 347: 2141-2148 [Full Text]
Berclaz, P.-Y., Zsengeller, Z., Shibata, Y., Otake, K., Strasbaugh, S., Whitsett, J. A., Trapnell, B. C. (2002). Endocytic Internalization of Adenovirus, Nonspecific Phagocytosis, and Cytoskeletal Organization Are Coordinately Regulated in Alveolar Macrophages by GM-CSF and PU.1. J. Immunol. 169: 6332-6342 [Abstract] [Full Text]
Bonfield, T. L., Russell, D., Burgess, S., Malur, A., Kavuru, M. S., Thomassen, M. J. (2002). Autoantibodies against Granulocyte Macrophage Colony-Stimulating Factor Are Diagnostic for Pulmonary Alveolar Proteinosis. Am. J. Respir. Cell Mol. Bio. 27: 481-486 [Abstract] [Full Text]
Seymour, J. F., Presneill, J. J. (2002). Pulmonary Alveolar Proteinosis: Progress in the First 44 Years. Am. J. Respir. Crit. Care Med. 166: 215-235 [Abstract] [Full Text]
Homer, R. J., Zheng, T., Chupp, G., He, S., Zhu, Z., Chen, Q., Ma, B., Hite, R. D., Gobran, L. I., Rooney, S. A., Elias, J. A. (2002). Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of chronic IL-13 exposure. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L52-L59 [Abstract] [Full Text]
Schoch, O D, Schanz, U, Koller, M, Nakata, K, Seymour, J F, Russi, E W, Boehler, A (2002). BAL findings in a patient with pulmonary alveolar proteinosis successfully treated with GM-CSF. Thorax 57: 277-280 [Abstract] [Full Text]
Carraway, M. S., Piantadosi, C. A., Wright, J. R. (2001). Alveolar proteinosis: a disease of mice and men. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L377-L378 [Full Text]
Gillessen, S., Mach, N., Small, C., Mihm, M., Dranoff, G. (2001). Overlapping roles for granulocyte-macrophage colony-stimulating factor and interleukin-3 in eosinophil homeostasis and contact hypersensitivity. Blood 97: 922-928 [Abstract] [Full Text]
SEYMOUR, J. F., PRESNEILL, J. J., SCHOCH, O. D., DOWNIE, G. H., MOORE, P. E., DOYLE, I. R., VINCENT, J. M., NAKATA, K., KITAMURA, T., LANGTON, D., PAIN, M. C., DUNN, A. R. (2001). Therapeutic Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Idiopathic Acquired Alveolar Proteinosis. Am. J. Respir. Crit. Care Med. 163: 524-531 [Abstract] [Full Text]
KITAMURA, T., UCHIDA, K., TANAKA, N., TSUCHIYA, T., WATANABE, J., YAMADA, Y., HANAOKA, K., SEYMOUR, J. F., SCHOCH, O. D., DOYLE, I., INOUE, Y., SAKATANI, M., KUDOH, S., AZUMA, A., NUKIWA, T., TOMITA, T., KATAGIRI, M., FUJITA, A., KURASHIMA, A., KANEGASAKI, S., NAKATA, K. (2000). Serological Diagnosis of Idiopathic Pulmonary Alveolar Proteinosis. Am. J. Respir. Crit. Care Med. 162: 658-662 [Abstract] [Full Text]
CARRAWAY, M. S., GHIO, A. J., CARTER, J. D., PIANTADOSI, C. A. (2000). Detection of Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Pulmonary Alveolar Proteinosis. Am. J. Respir. Crit. Care Med. 161: 1294-1299 [Abstract] [Full Text]