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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2547-2556. Prepublished online as a Blood First Edition Paper on October 9, 2008; DOI 10.1182/blood-2008-05-155689. This Article Full Text (PDF) Supplemental Results. Table, and Figures All Versions of this Article: blood-2008-05-155689v1 113/11/2547    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Uchida, K. Articles by Trapnell, B. C. Search for Related Content PubMed PubMed Citation Articles by Uchida, K. Articles by Trapnell, B. C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 5, 2008 Accepted September 3, 2008 Granulocyte/macrophage colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy individuals Kanji Uchida, Koh Nakata, Takuji Suzuki, Maurizio Luisetti, Masato Watanabe, Diana E. Koch, Carrie A. Stevens, Dave C. Beck, Lee A. Denson, Brenna C. Carey, Naoto Keicho, Jeffrey P. Krischer, Yoshitsugu Yamada, and Bruce C. Trapnell* Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata-shi, Niigata, Japan Institute for Respiratory Disease, San Matteo Hospital Foundation for Research and Care, University of Pavia, Pavia, Italy Translational Research Trials Office, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States Division of Gasteroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Department of Respiratory Diseases, International Medical Center of Japan, Shinjuko-ku, Tokyo, Japan Division of Informatics and Biostatistics, University of South Florida, Tampa, FL, United States Department of Anesthesiology, University of Tokyo, Bunkyo-ku, Tokyo, Japan Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States * Corresponding author; email: bruce.trapnell{at}cchmc.org. High levels of granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies are thought to cause pulmonary alveolar proteinosis (PAP), a rare syndrome characterized by myeloid dysfunction resulting in pulmonary surfactant accumulation and respiratory failure. Paradoxically, GM-CSF autoantibodies have been reported to occur rarely in healthy people and routinely in pharmaceutical intravenous immunoglobulin (IVIG)purified from serum pooled from healthy individuals. These findings suggest that either GM-CSF autoantibodies are normally present in healthy individuals at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic individuals with high levels of GM-CSF autoantibodies. Using several experimental approaches, GM-CSF autoantibodies were detected in all healthy individuals evaluated (n=72)at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GM-CSF was more abundant than previously reported but more that 99% was bound and neutralized by GM-CSF autoantibody. The critical threshold of GM-CSF autoantibodies associated with the development of PAP was determined. Results demonstrate that free serum GM-CSF is tightly maintained at low levels, identify a novel potential mechanism of innate immune regulation, help define the therapeutic window for potential clinical use of GM-CSF autoantibodies to treat inflammatory and autoimmune diseases, and have implications for the pathogenesis of PAP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S Saha, C Doe, V Mistry, S Siddiqui, D Parker, M Sleeman, E S Cohen, and C E Brightling Granulocyte-macrophage colony-stimulating factor expression in induced sputum and bronchial mucosa in asthma and COPD Thorax, August 1, 2009; 64(8): 671 - 676. [Abstract] [Full Text] [PDF]

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