title: Serum neutralizing capacity of GM-CSF reflects disease severity in a patient with pulmonary alveolar proteinosis successfully treated with inhaled GM-CSF.
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.
authors.affiliation: Department of Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka 591 8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Tazawa
authors.initials: T
authors.lastname: Ryushi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
mesh_terms: D000280:Administration, Inhalation; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor