Figures
- FIGURE 1
Distribution of the concentration of granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) in serum samples in the training study. a) A bee swarm plot of the serum GMAb concentrations in 78 patients with autoimmune pulmonary alveolar proteinosis (aPAP) and 90 healthy controls (HC) measured using the newly developed GMAb measuring kit (MBL2490023). b) A histogram of logarithmic serum concentrations in the same patients and healthy subjects as shown in (a).
- FIGURE 2
Comparison of the performance of ELISA between the newly developed kit and the conventional method. Granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) concentrations measured a) by the modified conventional ELISA kit or b) by the newly developed ELISA kit in the sera from 90 healthy subjects that were previously incubated with or without excess recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) (50 mg·mL−1). c) The correlation coefficient of the concentrations between the newly developed and the conventional methods was 0.80 in the healthy subjects and 0.95 in the patients with autoimmune pulmonary alveolar proteinosis. d) Receiver operating characteristic curve analysis (area under the curve 1.0).
- FIGURE 3
Estimation of the cut-off value between the healthy subjects and the patients using the logistic regression methods.
- FIGURE 4
Verification of the cut-off value (1.65 U·mL−1) using data obtained from the sera of patients with autoimmune (aPAP) (n=213), secondary (sPAP) (n=40) and hereditary pulmonary alveolar proteinosis (hPAP) (n=5), and other lung diseases (h=162). GMAb: granulocyte–macrophage colony-stimulating factor autoantibody.
- FIGURE 5
Exclusive plots for a) granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) versus anti-melanoma differentiation-associated protein (MDA)-5 antibody (Ab), b) GMAb versus anti-aminoacyl transfer RNA synthetase (ARS) Ab and c) anti-MDA-5 Ab versus anti-ARS Ab. Red: autoimmune pulmonary alveolar proteinosis; blue: other patients.
Tables
- TABLE 1
Demographic data of subjects in the training study
Characteristics Healthy subjects aPAP patients Subjects n 90 78 Male/female n 37/53 32/46 Age years mean±sd 56.4±14.1 58.7±12.3 Asian/Caucasian n 22/68 78/0 Serum GMAb concentration U·mL−1 Mean±sd 0.151±0.109 90.95±123.0 Maximum 0.71 718.7 Minimum 0.018 2.59 aPAP: autoimmune pulmonary alveolar proteinosis; GMAb: granulocyte–macrophage colony-stimulating factor autoantibody.
- TABLE 2
Demographic data of cases in the validation study
Characteristics aPAP sPAP hPAP Other lung diseases Subjects n 213 40 5 162 Male/female n 122/60 19/21 0/5 86/75 Age years mean±sd 52.6±14.7 57.6±13.3 56.4±14.5 66.2±12.0 Asian/Caucasian n 213/0 40/0 5/0 162/0 Serum GMAb concentration U·mL−1 Mean±sd 103.6±127.5 0.191±0.302 0.148±0.141 0.517±.818 Maximum 899.9 1.9 0.38 48.57 Minimum 5.59 0.04 0.02 0.01 Diagnostic procedures n BAL 213 36 5 144 VATS 0 4 0 17 Autopsy 0 0 0 1 Other lung diseases n CTD 45 DIPD 20 IIPs 60 IPF 8 Other IIPs 52 Infectious disease 19 Miscellaneous 18 Connective tissue disease (CTD) cases included five amyopathic dermatomyositis cases, 11 polymyositis/dermatomyositis interstitial lung diseases, 11 rheumatoid arthritis cases, four Sjögren syndromes, five systemic scleroses and nine other diseases. Infectious disease cases included eight Pneumocystis pneumonias, four bacterial pneumonias, three influenza pneumonias and four other infectious diseases. Miscellaneous diseases included four alveolar haemorrhages, three chronic eosinophilic pneumonias, two acute respiratory distress syndromes, two chronic hypersensitivity pneumonias and seven other diseases. aPAP: autoimmune pulmonary alveolar proteinosis; sPAP: secondary pulmonary alveolar proteinosis; hPAP: hereditary pulmonary alveolar proteinosis; GMAb: granulocyte–macrophage colony-stimulating factor autoantibody; BAL: bronchoalveolar lavage; VATS: video-assisted thoracic surgery; DIPD: drug-induced pulmonary disease; IIP: idiopathic interstitial pneumonia; IPF: idiopathic pulmonary fibrosis.
- TABLE 3
Demographic characteristics of patients with granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) >1.65 U·mL−1
Case Age years Sex Diagnosis GMAb U·mL−1 Anti-MDA-5 Ab Anti-ARS Ab 1 63 M sPAP (MDS) 1.90 Negative Negative 2 76 F IIPs 2.56 Negative Negative 3 75 M CTD 48.57 Negative Negative 4 68 M CTD 2.85 Negative Negative 5 73 F IIPs 2.85 Negative Negative MDA: melanoma differentiation-associated protein; Ab: antibody; ARS: aminoacyl transfer RNA synthetase; M: male; F: female; sPAP: secondary pulmonary alveolar proteinosis; MDS: myelodysplastic syndrome; IIP: idiopathic interstitial pneumonia; CTD: connective tissue disease.
Supplementary Material
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Supplementary material 00259-2019.supp
Figure S1 00259-2019.figureS1
Figure S2 00259-2019.figureS2
Figure S3 00259-2019.figureS3
Figure S4 00259-2019.figureS4
Figure S5 00259-2019.figureS5
