Abstract
KL-6 and IL-18 have been investigated as potential lung-specific biomarkers in different types of interstitial lung disease (ILD), including systemic sclerosis (SSc). However, their predictive significance for ILD detection, progression, and mortality remains unclear. The study aimed to assess the discriminative capabilities of KL-6 and IL-18 in differentiating between various grades of fibrosis identified through semiquantitative CT extension in SSc-ILD and compare the diagnostic performance of these biomarkers with traditional pulmonary function tests, and evaluate the significance concerning ILD progression and short-term lung volume changes and mortality.
Baseline and follow-up measurements were retrieved at 12-18 months of chest high-resolution computed tomography scans and pulmonary function tests. The annualized rate of change in forced vital capacity (FVC%) from baseline to follow-up served as a surrogate outcome for ILD progression. Serum concentrations of KL-6 and IL-18 were quantified using established quantitative ELISA techniques. We examined the sensitivity and specificity of various cut-off values of serum KL-6, IL-18, %DLCO, and %FVC annualized change for predicting survival.
A correlation was found between semiquantitative CT grade and KL-6 (β = 0.78, p = 0.01) and IL-18 (β = 0.62, p = 0.03). ROC analysis established optimal cut-off values for KL-6 (273.80 U/mL) and IL-18 (290.83 U/mL) in detecting ILD presence. The area under the curve (AUC) values for KL-6 and IL-18 outperformed FVC% and DLCO%, particularly in discriminating grade 2 from grade 1 ILD. During follow-up, 7 patients (9.5%) died. KL-6 levels at baseline were predictive of faster %FVC decline (β=-0.34, p = 0.006) and %DLCO (β=-0.24,p=0.04) at 1-year follow-up. IL-18 levels at baseline were predictive of a faster %FVC decline (β=-0.24, p = 0.04) but not a %DLCO decline. A significant correlation between mortality and KL-6 (β = 0.32, p = 0.003), %DLCO (β = 0.57, p = 0.003), and %FVC (β = 0.62, p = 0.002) was found. %DLCO showed the best performance in predicting mortality compared to the other biomarkers. ROC analysis showed 668.34 U/mL the KL-6 serum concentration for predicting mortality in SSc.
KL-6 and IL-18 are robust predictors of ILD progression in SSc, with independent associations with short-term lung volume changes. Notably, %DLCO emerges as a superior predictor of mortality compared to KL-6 and IL-18, offering a valuable tool for risk stratification in SSc patients.
C. Sieiro Santos: None. M. Retuerto: None. L. Sierra: None. S. Calleja Antolín: None. E. Bollo de Miguel: None. J. Ordas Martínez: None. J. de la Calle Lorenzo: None. E. Díez Álvarez: None.
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