{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department 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",
    "Medical Research Center, Tianjian Laboratory of Advanced Biomedical Sciences, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou University",
    "Guangzhou National Laboratory",
    "Feichuang Biomedical Technology (Guangzhou) Co., Ltd",
    "Guangzhou Jinyu Medical Laboratory Group Co., Ltd",
    "Department of Rheumatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University",
    "Department of Radiation Medicine, Faculty of Preventive Medicine, Fourth Military Medical University",
    "Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University",
    "Department of Rheumatology, Dongguan People’s Hospital"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huimin Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruogu Lai"
    },
    {
      "affs": [
        1
      ],
      "name": "Junqi Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Qian Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Yunpeng Xiao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinru Wei"
    },
    {
      "affs": [
        4
      ],
      "name": "Jin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanting Fang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunxin Lai"
    },
    {
      "affs": [
        3
      ],
      "name": "Ping Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Xiaoxiao Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Jie Zhang"
    },
    {
      "affs": [
        7
      ],
      "name": "Shuilian Yu"
    },
    {
      "affs": [
        8
      ],
      "name": "Fei Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Baoqing Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Jin Su"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7k2kxkc8p6kfw.bib",
  "cited_by": 0,
  "doi": "10.1186/s12931-026-03816-x",
  "fulltext_url": "https://doi.org/10.1186/s12931-026-03816-x",
  "id": "7k2kxkc8p6kfw",
  "issns": [
    "1465-993X",
    "1465-9921"
  ],
  "landing_url": "https://doi.org/10.1186/s12931-026-03816-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC705-779"
    ],
    [
      "openalex",
      "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis"
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  "openalex": "W7171544932",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/7k2kxkc8p6kfw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:27Z",
      "native_id": "e470766548244014a18d974f1fbff6e7",
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      "url": "https://doi.org/10.1186/s12931-026-03816-x"
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis",
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  ],
  "title": "Exosomal KL-6 surpasses total plasma KL-6 in the diagnosis of Interstitial Lung Disease (ILD)",
  "title_text": "Exosomal KL-6 surpasses total plasma KL-6 in the diagnosis of Interstitial Lung Disease (ILD)",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:27Z",
  "url": "https://research.draconitic.com/paper/7k2kxkc8p6kfw",
  "venue": "Respiratory Research",
  "versions": []
}