Serum YKL‐40 is a reliable biomarker for pulmonary alveolar proteinosis
2017
Background and objective
Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP.
Methods
A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1−329 and −131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed.
Results
Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P < 0.0001; 323 ± 36 ng/mL vs 3 ± 1 ng/mL, P < 0.0001, respectively). Serum YKL-40 levels correlated with diffusing capacity of the lung for carbon monoxide (DLCO ) at baseline (P = 0.002) and over time (P < 0.0001). Patients with disease progression had higher baseline serum YKL-40 levels than those who remained stable or improved (P < 0.0001). A baseline cut-off level of 300 ng/mL was predictive of disease progression (HR (hazard ratio): 7.875, P = 0.001). The presence of the G allele was associated with higher serum and BALF levels of YKL-40.
Conclusion
YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP.
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