Serum KL-6 combined with immune/inflammatory biomarkers identifies complicated silicosis

Complicated silicosis (CS) poses significant diagnostic challenges, with current diagnosis relying heavily on radiographic imaging. These challenges highlight a need for reliable non-invasive biomarkers to improve early detection and disease staging. This study aimed to evaluate serum Krebs von den Lungen-6 (KL-6) levels in silicosis patients across different disease stages and explore their association with immune-inflammatory markers to assess its potential as a biomarker for early diagnosis and risk stratification. This study enrolled individuals evaluated at our institution between October 2022 and June 2025 and categorized them into three groups: dust-exposed workers without silicosis (DEWs), patients with simple silicosis (SS), and those with CS. Serum levels of KL-6, interleukin (IL)-6, IL-8, IL-10, CD8+ T cells, and other inflammatory markers were measured, and the erythrocyte sedimentation rate (ESR) was assessed alongside pulmonary function tests. Receiver operating characteristic (ROC) curves and correlation analyses were used to assess diagnostic performance and biomarker associations. In total, 135 individuals were enrolled in this study. Of these, 25 were categorized as DEWs, 33 as patients with SS, and 77 with CS. Patients with CS were younger than those with SS (median age: 59.0 vs. 68.0 years) and had a shorter exposure duration (mean: 16 vs. 18 years) but worse lung function. KL-6 levels increased progressively across groups, peaking in the CS group (SS vs. CS: median, 257.00 vs. 441.22 U/mL; IQR: 202.96–358.50 vs. 295.53–926.50 U/mL). KL-6 was negatively correlated with FVC%, FEV1%, and DLCO% and positively correlated with lactate dehydrogenase (LDH) (r = 0.57) and ESR (r = 0.44). At a cutoff of 300 U/mL, KL-6 distinguished CS from SS with an area under the curve (AUC) of 0.756 (sensitivity, 75.3%; specificity, 69.7%) and performed better in distinguishing CS from DEWs (AUC = 0.842; sensitivity, 74%; specificity, 84%). A combined model of KL-6, LDH, and ESR further improved diagnostic accuracy (AUC = 0.914; sensitivity, 85.7%; specificity, 80.0%). Serum KL-6 is strongly associated with pulmonary function decline and systemic inflammation in silicosis. When combined with LDH and ESR, it significantly enhances diagnostic precision, offering a promising non-radiological biomarker panel for disease staging and early identification of disease severity.