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 GX-CSF in surfactant; homeostasis and disease pathogenesis Based on murine data, GM-CSF therapy was administered to PAP patients, with a subset 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, nentralizing anti-GAI-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 GH-CSF therapy. In addition, we presenting data from a patient undergoing PlasmaPheresis n which anti-GM-CSF titer decreased with improv these data support the Together in the lung disease, hypothesis that PAP is an anti-GM-CSF autoimmune disease due to the development of antibodies, which results in the deactivation or neutralization of GmCSF. (C) 2002 Elsevier Science (USA).