ArticleRespiratory research2026
Exosomal KL-6 surpasses total plasma KL-6 in the diagnosis of Interstitial Lung Disease (ILD).
Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundKrebs 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.
methodsWe 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.
resultsSingle-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.
conclusionsExosomal 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.
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