Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects

Kanji Uchida, Koh Nakata, Takuji Suzuki, Maurizio Luisetti, Masato Watanabe, Diana E. Koch, Carrie A. Stevens, David C. Beck, Lee A. Denson, Brenna C. Carey, Naoto Keicho, Jeffrey P. Krischer, Yoshitsugu Yamada, Bruce C. Trapnell

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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 autoan- tibodies 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.

Original languageEnglish
Pages (from-to)2547-2556
Number of pages10
JournalBlood
Volume113
Issue number11
DOIs
Publication statusPublished - Mar 12 2009

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Myeloid Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Autoantibodies
Healthy Volunteers
Pulmonary Alveolar Proteinosis
Intravenous Immunoglobulins
Serum
Pulmonary Surfactants
Respiratory Insufficiency
Autoimmune Diseases
Purification

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Uchida, K., Nakata, K., Suzuki, T., Luisetti, M., Watanabe, M., Koch, D. E., ... Trapnell, B. C. (2009). Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. Blood, 113(11), 2547-2556. https://doi.org/10.1182/blood-2009-05-155689

Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. / Uchida, Kanji; Nakata, Koh; Suzuki, Takuji; Luisetti, Maurizio; Watanabe, Masato; Koch, Diana E.; Stevens, Carrie A.; Beck, David C.; Denson, Lee A.; Carey, Brenna C.; Keicho, Naoto; Krischer, Jeffrey P.; Yamada, Yoshitsugu; Trapnell, Bruce C.

In: Blood, Vol. 113, No. 11, 12.03.2009, p. 2547-2556.

Research output: Contribution to journalArticle

Uchida, K, Nakata, K, Suzuki, T, Luisetti, M, Watanabe, M, Koch, DE, Stevens, CA, Beck, DC, Denson, LA, Carey, BC, Keicho, N, Krischer, JP, Yamada, Y & Trapnell, BC 2009, 'Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects', Blood, vol. 113, no. 11, pp. 2547-2556. https://doi.org/10.1182/blood-2009-05-155689
Uchida, Kanji ; Nakata, Koh ; Suzuki, Takuji ; Luisetti, Maurizio ; Watanabe, Masato ; Koch, Diana E. ; Stevens, Carrie A. ; Beck, David C. ; Denson, Lee A. ; Carey, Brenna C. ; Keicho, Naoto ; Krischer, Jeffrey P. ; Yamada, Yoshitsugu ; Trapnell, Bruce C. / Granulocyte/macrophage-colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects. In: Blood. 2009 ; Vol. 113, No. 11. pp. 2547-2556.
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