Serological diagnosis of idiopathic pulmonary alveolar proteinosis

Previously, we reported the specific occurrence of neutralizing autoantibod ies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in th e bronchoalveolar ravage fluid from 11 Japanese patients with idiopathic pu lmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence o f the autoantibody is not limited to the Japanese patients, we examined ser a from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detectio n of the autoantibody in sera can be used for diagnosis of I-PAP. To establ ish a simple and convenient method for diagnosis of I-PAP, we developed a n ovel latex agglutination test using latex beads coupled with recombinant hu man CM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determine d by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 4 0 normal subjects. These results establish that the latex agglutination tes t is a reliable method for serological diagnosis of I-PAP with high sensiti vity (100%) and specificity (98%).