Autoantibody against granulocyte-macrophage colony-stimulating factor and other serum markers in pulmonary alveolar proteinosis

Objective: To evaluate the application of serum markers in the diagnosis, monitoring and understanding of the mechanisms of pulmonary alveolar proteinosis (PAP), the levels of the autoantibody against granulocyte-macrophage colony-stimulating factor (anti-GM-CSF antibody), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other serum markers, lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA), were measured in patients with PAP.

Methods: Serum samples were taken from 17 PAP patients (16 idiopathic and 1 congenital PAP), 18 patients with other pulmonary diseases disease control) and 40 healthy volunteers (healthy control). Anti-GM-CSF antibody was measured with indirect enzyme-linked immunosorbent assay (ELISA). GM-CSF and CEA were measured with commercial ELISA kits. LDH was measured with a kinetic method.

Results: The absorbance at 450 nm of serum anti-GM-CSF antibody in the idiopathic PAP (I-PAP), disease control and healthy control were 1.263 +/- 0.047, 0.835 +/- 0.018 and 0.246 +/- 0.009 respectively. The sensitivity and specificity of anti-GM-CSF in the diagnosis of I-PAP were 93.8% and 100% respectively, if the cutpoint was set as 4 times the average value of the healthy control. GM-CSF was not detectable in most PAP and other samples except 3/17 of PAP and 1/19 of disease control. The serum level of LDH was increased in I-PAP patients and correlated with CEA (r = 0.518) and alveolar-artery oxygen gradient (r = 0.769). CEA was increased in I-PAP patients [(12.85 +/- 3.79) ng/ml] compared with disease control [(2.04 +/- 0.63) ng/ml] and health control [(1.46 +/- 0.34) ng/ml] and correlated with alveolar-artery oxygen gradient (r = 0.552). The LDH levels decreased after lavage therapy [(348.38 +/- 38.88), (242.88 +/- 30.71) U/L, P < 0.05].

Conclusions: The high sensitivity and specificity of anti-GM-CSF antibody make it a potential diagnostic serum marker for I-PAP. LDH and CEA are useful markers in evaluation of disease progression of PAP.