Serum neutralizing capacity of GM-CSF reflects disease severity in a patient with pulmonary alveolar proteinosis successfully treated with inhaled GM-CSF

Respir Med. 2004 Dec;98(12):1227-30. doi: 10.1016/j.rmed.2004.08.011.

Abstract

Existence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody and treatment with recombinant GM-CSF are new topics in idiopathic pulmonary alveolar proteinosis (PAP). We have hypothesized inhaled GM-CSF is effective and neutralizing capacity of GM-CSF, not concentration of anti-GM-CSF antibody in serum reflect disease severity. A 57-year-old female smoker with idiopathic PAP was treated with inhaled GM-CSF. The response to the treatment was evaluated by diffusing capacity for carbon monoxide (DLCO), alveolar-arterial oxygen gradient ([A-a]DO2). Conventional serum markers, including KL-6, surfactant apoprotein (SP)-A, SP-D, carcino-embryonic antigen and cytokeratin fragment 19 (CYFRA), and concentration of anti-GM-CSF antibody were examined. The neutralizing capacity of GM-CSF in serum was evaluated using a GM-CSF dependent cell line, TF-1. Ground glass opacity disappeared at the end of the treatment. Her DLCO, [A-a]DO2 remarkably improved after treatment. The neutralizing capacity of GM-CSF declined in line with disease remission and it correlated significantly with DLCO (P = 0.0137). The concentration of anti-GM-CSF antibody had no significant relation with disease severity and serum markers including neutralizing capacity. Conventional serum markers other than CYFRA showed no significant correlation with Inhaled GM-CSF was effective for idiopathic PAR Serial measurement of neutralizing capacity of GM-CSF was useful to evaluate disease severity and the anti-GM-CSF antibody was proved to be a causative factor for PAR In the future, inhaled GM-CSF may replace whole lung lavage and response to GM-CSF and its optimal amount may be decided by the capacity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Middle Aged
  • Pulmonary Alveolar Proteinosis / drug therapy*
  • Pulmonary Alveolar Proteinosis / immunology
  • Recombinant Proteins
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Autoantibodies
  • Biomarkers
  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor