Circulating biomarkers and their potential utility in pulmonary alveolar proteinosis (PAP)
| Biomarker | Biologic function/origin | Association in PAP |
|---|---|---|
| Diagnosis | ||
| GM-CSF autoantibody | Neutralise circulating GM-CSF/present also in healthy patients at low titre (<1 μg·ml–1) | Diagnostic for autoimmune PAP [93] |
| GM-CSF | Growth factor for granulocytes–macrophages/AM | Increased serum level in hereditary PAP, in presence of normal serum GM-CSF autoantibody level [102] |
| Disease activity, outcome and response to treatment | ||
| LDH | Marker of cellular death/all cell types | PA–aO2 and VC [3, 105, 106] |
| CYFRA21-1 | Tumour tissue antigen/mostly epithelial cells | PaO2, FEV1, DLCO and HRCT score [106, 107] |
| CEA | Tumour tissue antigen/mostly epithelial cells | PaO2, FEV1, DLCO and HRCT score [106, 107] |
| NSE | Tumour tissue antigen/neuroendocrine cells | LDH, disease activity [106, 107] |
| KL-6 | Mucin 1, host defence/type II pneumocytes | PA–aO2, DLCO, VC, TLC and PaO2, response to treatment (WLL) [2, 108–110] |
| SP-A | Surfactant protein, host defence of the lung/type II pneumocytes | Alveolar type II cell hyperplasia [111] |
| SP-D | Surfactant protein, host defence of the lung/type II pneumocytes | Alveolar type II cell hyperplasia [111] |
| YKL-40 | Chitinase-like protein/AM | DLCO, disease outcome [113, 114] |
| MCP | Monocyte chemotactic proteins/mostly epithelial cells | Mononuclear chemoattractant activity and CCR2 receptor suppression on macrophages [115] |
AM: alveolar macrophages; CEA: carcinoembryonic antigen; CCR2: C-C chemokine receptor type 2; CYFRA: cytokeratin-fragment; DLCO: diffusing capacity of the lung for carbon monoxide; FEV1: forced expiratory volume in 1 s; GM-CSF: granulocyte–macrophage colony-stimulating factor; HRCT: high-resolution computed tomography; KL-6: Krebs von den Lungen 6; LDH: lactate dehydrogenase; MCP: monocyte chemoattractant protein-1; NSE: neuron-specific enolase; PaO2: arterial oxygen tension; PA–aO2: alveolar–arterial oxygen tension difference; SP: surfactant protein; TLC: total lung capacity; VC: vital capacity; WLL: Whole lung lavage; YKL-40: chitinase 3-like 1 protein.