Anti-GM-CSF Titer Predicts Response to GM-CSF Therapy in Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is an idiopathic disease characterized by the accumulation of surfactant in the pulmonary airspaces. The development of a PAP-like syndrome in the GM-CSF knockout mouse and resolution of disease by local GM-CSF expression strongly implicates GM-CSF in surfactant...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2002-12, Vol.105 (3), p.342-350
Main Authors: Bonfield, Tracey L., Kavuru, Mani S., Thomassen, Mary Jane
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antibodies - analysis
Biological and medical sciences
Enzyme-Linked Immunosorbent Assay
Female
Granulocyte-Macrophage Colony-Stimulating Factor - immunology
Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use
Humans
Leukocyte Count
Male
Medical sciences
Middle Aged
Plasmapheresis
Pneumology
Pulmonary Alveolar Proteinosis - drug therapy
Pulmonary Alveolar Proteinosis - immunology
Respiratory system : syndromes and miscellaneous diseases
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Summary:Pulmonary alveolar proteinosis (PAP) is an idiopathic disease characterized by the accumulation of surfactant in the pulmonary airspaces. The development of a PAP-like syndrome in the GM-CSF knockout mouse and resolution of disease by local GM-CSF expression strongly implicates GM-CSF in surfactant homeostasis and disease pathogenesis. Based on murine data, GM-CSF therapy was administered to PAP patients, with a subset responding to therapy. The lack of response to GM-CSF therapy in some patients is unexplained. In adult idiopathic PAP there appears to be no intrinsic cellular defect in synthesizing or secreting GM-CSF and/or function in the GM-CSF receptor. Subsequent studies have shown the presence of circulating, neutralizing anti-GM-CSF antibodies in all adult PAP patients studied to date. Whether the anti-GM-CSF is causally related to the PAP disease and whether it should be the target of manipulation remains to be determined. The present study quantified the anti-GM-CSF levels sequentially in PAP patients receiving GM-CSF therapy. The data indicate that titers of circulating anti-GM-CSF predict response to GM-CSF therapy. In addition, we present data from a patient undergoing plasmapheresis in which anti-GM-CSF titer decreased with improvement in the lung disease. Together, these data support the hypothesis that PAP is an anti-GM-CSF autoimmune disease due to the development of antibodies, which results in the deactivation or neutralization of GM-CSF.
ISSN:1521-6616
1521-7035
DOI:10.1006/clim.2002.5301