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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 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 Citation Map 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. Related Collections Immunobiology Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS Granulocyte/macrophage–colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects Kanji Uchida1,2, Koh Nakata3, Takuji Suzuki1, Maurizio Luisetti4, Masato Watanabe3, Diana E. Koch1, Carrie A. Stevens5, David C. Beck1,6, Lee A. Denson7, Brenna C. Carey1, Naoto Keicho8, Jeffrey P. Krischer9, Yoshitsugu Yamada2, and Bruce C. Trapnell1,6,10 1 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, OH; 2 Department of Anesthesiology, University of Tokyo, Tokyo, Japan; 3 Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan; 4 Institute for Respiratory Disease, San Matteo Hospital Foundation for Research and Care, University of Pavia, Pavia, Italy; 5 Translational Research Trials Office, Cincinnati Children's Hospital Medical Center, OH; 6 Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, OH; 7 Division of Gastroenterology, Cincinnati Children's Hospital Medical Center, OH; 8 Department of Respiratory Diseases, International Medical Center of Japan, Tokyo, Japan; 9 Division of Informatics and Biostatistics, University of South Florida, Tampa; and 10 Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, OH 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 subjects. These findings suggest that either GM-CSF autoantibodies are normally present in healthy people at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic persons with high levels of GM-CSF autoantibodies. Using several experimental approaches, GM-CSF autoantibodies were detected in all healthy subjects evaluated (n = 72) at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GM-CSF was more abundant than previously reported, but more than 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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