Serum YKL-40 as a candidate biomarker for hypersensitivity pneumonitis
Background: YKL-40, a chitinase-like protein mainly secreted by macrophages, is increased in serum of several interstitial lung diseases (ILD) and sarcoidosis. The role of YKL-40 as biomarker in hypersensitivity pneumonitis (HP), a T-cell-driven granulomatous lung disease, is still unknown. The aim of our study was to evaluate the role of serum YKL-40 as biomarker for HP.
Patients and methods: 175 ILD patients (75 HP, 21 COP, 34 iNSIP and 45 IPF) and 60 healthy controls (HC) were studied retrospectively. Serum YKL-40 was measured by ELISA at baseline and in 39 HP patients in follow up. We evaluated the correlation between initial YKL-40 levels, clinical variables and pulmonary function. Serum LDH was compared. Disease progression was defined as deterioration of symptoms, pulmonary function tests or chest imaging based on a 6 months follow up.
Results: Mean serum YKL-40 level in HP patients was 127 ± 9 ng/ml, significantly elevated compared to HC (39 ± 4 ng/ml, p < 0.001) and lower than in iNSIP, COP and IPF (184 ± 21, 213 ± 33 and 214 ± 20 ng/ml, p < 0.05 for all comparisons). Initial serum YKL-40 levels correlated inversely with baseline FVC, FEV1 and DLco (r=-0.376, p = 0.002; r=-0.322, p = 0.007 and r=-0.330, p = 0.005; respectively) and directly with serum LDHlevels (r= 0.558, p < 0.001). Longitudinal changes in serum YKL-40 correlated with DLco and LDH changes over time (r=-0.579, p < 0.001; r= 0.770, p < 0.001; respectively). HP patients with disease progression (n= 32) had higher serum YKL-40 levels than those without (167 ± 12 vs. 98 ± 11 ng/ml, p < 0.001). At a cut-off level of 119 ng/ml, serum YKL-40 predicted disease progression with 81% Se, 77% Sp and 79% accuracy. Serum LDH showed similar results (Se 75%, Sp 81% and accuracy 79%). The combined assessment of serum YKL-40 and LDH performed better (Se 81%, Sp 91%, accuracy 80%).
Conclusion: Serum YKL-40, alone or in combination with LDH, seems to be a promising biomarker for HP.