YKL-40 and KL-6 in the differential diagnosis of interstitial lung disease

Interstitial lung diseases (ILD) are a group of diffuse the lung diseases that cause inflammation and fibrosis of the lung parenchyma. There is an ongoing search for specific biomarkers of ILD that would provide early detection of the disease, differentiate between specific etiologies and guide follow up that is affordable and available. KL-6 is a protein produced by type 2 pneumocytes in the lung. On the other hand, YKL-40 is a promising marker in many diseases with chronic inflammation in the family of chitinase-like proteins. As ILD pathogenesis is largely a chronic inflammatory process, we hypothetized that YKL-40 could be increased in these diseases. We also compared YKL-40 with KL-6, a marker used in ILD for years. Patients diagnosed with idiopathic pulmonary fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis and connective tissue disease-ILD who were admitted to our clinic between April 2019 and February 2020 were included in our study. Blood samples were collected from patients and an age and sex matched control group without lung disease and analyzed for KL-6 and YKL-40 with ELISA method. Demographic parameters, clinical features, blood chemistry and lung function data were recorded. Median KL-6 and YKL-40 values of all study groups were higher than the control group, however only the difference between IPF and control group was statistically significant. Cut-off value for KL-6 in the IPF and control group was 74.75 U/mL (p<0,001; Sensitivity= 76.19%, Specifity= 90%), while the cut-off point for YKL-40 was 27.96 ng/mL (p<0.001; Sensitivity= 95.24%, Specificity= 70%). There was a significant correlation between KL-6 and YKL-40 (p<0.05; r=0.951). KL-6 and YKL-40 did not differ between genders and were not correlated with age. Both markers were higher in smokers than smokers. Serum KL-6 and YKL-40 values were higher in individuals with clubbing compared to individuals without clubbing. KL-6 and YKL-40 levels were negatively correlated with oxygen saturation. Both markers are elevated in IPF however their role in follow-up, evaluation of treatment response and prognosis needs to be evaluated in larger patient populations.