Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor.
Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.
Kitamura
T
T
The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Tanaka
N
N
Watanabe
J
J
Uchida
Kanegasaki
S
S
Yamada
Y
Y
Nakata
K
K
D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D011649:Pulmonary Alveolar Proteinosis / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D016178:Granulocyte-Macrophage Colony-Stimulating Factor