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Updated: Oct 25, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Exosomal KL-6 surpasses total plasma KL-6 in the diagnosis of Interstitial Lung Disease (ILD)
Huimin Huang1,2, Ruogu Lai1, Junqi Li3
1Department of Clinical Laboratory, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 28 Qiaozhong Road, Liwan District, Guangzhou, Guangdong, 510120, China.
Background:
Krebs Von den Lungen-6 (KL-6) is an established biomarker for interstitial lung diseases (ILDs), but the utility of exosomal KL-6 versus plasma KL-6 in connective tissue disease-associated ILD (CTD-ILD) remains unclear.
Methods:
We integrated single-cell transcriptomic re-analysis (GSE135893) with a multi-center cohort of 223 subjects, including 167 ILD, 22 CTD without ILD[CTD (Non-ILD)], 34 healthy controls(HCs). Plasma and exosomal KL-6 were measured, and diagnostic performance was evaluated via Receiver operating characteristic(ROC) analysis. Ten progressive ILD patients were monitored longitudinally.
Results:
Single-cell sequencing revealed a significantly stronger correlation between Mucin 1 (MUC1)and exosomal markers (CD63/CD81) in alveolar type II cells from ILD patients compared to HCs, suggesting a potential vesicular association of KL-6. Clinical validation demonstrated that both plasma and exosomal KL-6 levels were significantly elevated in the ILD group. Crucially, for distinguishing CTD-ILD patients with negative plasma KL-6 results [CTD-ILD (plasma KL-6-)] from HCs, exosomal KL-6 [Area under the curve(AUC) = 0.900] outperformed plasma KL-6 (AUC = 0.879). More importantly, in differentiating CTD-ILD (plasma KL-6-) from CTD (Non-ILD), exosomal KL-6 again showed superior diagnostic accuracy (AUC = 0.782, sensitivity = 90.0%, specificity = 77.3%) compared to plasma KL-6 (AUC = 0.705, sensitivity = 65.0%, specificity = 81.8%). Plasma and exosomal KL-6 concentrations were highly correlated (rs = 0.968, p < 0.001). In longitudinal monitoring, both biomarkers increased in patients with radiographic disease progression.
Conclusions:
Exosomal KL-6 is superior to plasma KL-6 for diagnosing CTD-ILD, especially in plasma KL-6-negative patients, and shows potential for monitoring disease progression.