Kinetic Changes in Serum KL-6 Levels Predict Disease Progression in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: A Retrospective Observational Study

Abstract

Background: The clinical course of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable. The Krebs von den Lungen-6 (KL-6) glycoprotein is a promising biomarker for reflectingepithelial injury. However, serum KL-6 and its association with the progression of SSc-ILD have been understudied. Methods: We reviewed 77 consecutive patients with SSc-ILD seen from 2004 to 2016. A longitudinal study of forced vital capacity (FVC), serum KL-6 levels, and the changes in KL-6 levels from baseline (ΔKL-6) was conducted. The progression of ILD was defined as ≥10% relative decline in FVC predicted or 5%–10% decline in FVC predicted along with radiological progression on chest computed tomography. The risk factors for ILD progression were assessed by univariate and multivariate regression.Results: The 77 study patients included 58 women (75%). The median age of the study patients was 56 years, and 59 (79%) patients had diffuse cutaneous SSc. During a 5-year follow-up period, 10 (13%) showed rapid progression of ILD within 2 years, 39 (51%) had overall progressionduring the 5 years, and 28 (36%) had stable disease. Most patients with progressive ILD showed elevationsin serum KL-6 levels over the initial 1-year follow-up period. The best cut-off value for ΔKL-6 that predicted progression of ILD was 193 U/mL (sensitivity 81.6%, specificity 92.9%). Multivariate analysis with adjustment revealed that diffuse cutaneous SSc(hazard ratio [HR] 3.1; 95% confidence interval [CI] 1.05-9.36]) and ΔKL-6 > 193 U/mL from baseline(HR, 4.7; 95% CI, 2.14-10.4)were independent predictors for progression of SSc-ILD.Conclusion: Changes in the KL-6 level can be useful for predicting disease progression in patients withSSc-ILD.