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Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study

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Abstract

Few biomarkers distinguish connective tissue disease-associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF). Latent transforming growth factor-β binding protein-2 (LTBP2), a secreted extracellular matrix protein, is involved in pulmonary fibrosis. However, the role of LTBP2 in differentially diagnosing CTD-ILD and IPF is unclear. In this study, enzyme-linked immunosorbent assays quantified plasma LTBP2 concentrations in 200 individuals (35 healthy controls, 42 CTD patients without ILD, 89 CTD-ILD patients, and 34 IPF patients). CTD-ILD and IPF were further classified based on chest imaging pattern and pulmonary function test results. Plasma LTBP2 levels were significantly elevated in the IPF group compared with the CTD-ILD group. ROC analysis further suggested the possible value of LTBP2 in differentially diagnosing CTD-ILD and IPF. Additionally, CTD-ILD patients with progressive lung fibrosis had higher plasma LTBP2 concentrations than those who did not. Similarly, patients with IPF developing acute exacerbation showed higher plasma LTBP2 levels than those with stable IPF. This is the first study showing that LTBP2 was closely associated with the usual interstitial pneumonia (UIP) pattern in rheumatoid arthritis-associated ILD (RA-ILD). Moreover, the optimal cutoff values of LTBP2 for distinguishing IPF from CTD-UIP/RA-UIP were 33.75 and 38.33 ng/mL with an AUC of 0.682 and 0.681, respectively. Our findings suggest that plasma LTBP2 levels may differentially diagnose CTD-ILD and IPF, and assess their fibrotic activity. Additionally, clinical LTBP2 evaluation may be a great aid to identifying the presence of the UIP pattern in RA-ILD and to discriminating IPF from CTD-UIP, particularly RA-UIP.

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Acknowledgments

Not applicable.

Funding

This work was supported by funds from the National Natural Science Foundation of China (Grant No: 82070062) and the Climbing Project for Medical Talent of Zhongnan Hospital, Wuhan University (Grant No. PDJH202205).

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Author notes

  1. Menglin Zou, Xingxing Hu and Weiwei Song have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China

    Menglin Zou, Xingxing Hu, Weiwei Song, Han Gao, Changrong Wu & Zhenshun Cheng

  2. Fourth Ward of Medical Care Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

    Menglin Zou

  3. Department of Respiratory and Critical Care Medicine, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China

    Weishuai Zheng

  4. Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China

    Zhenshun Cheng

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Contributions

ZC, WZ and CW designed this study. MZ, XH, WS, HG, CW, WZ, and ZC collected data and human blood samples. MZ, XH, WS and WZ performed experiments and analyzed the data. MZ and WZ wrote the original manuscript. MZ, XH and WS contributed equally to this study and shared first authorship. ZC, WZ and CW contributed equally to this study.

Corresponding authors

Correspondence to Changrong Wu, Weishuai Zheng or Zhenshun Cheng.

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The authors have no relevant financial or non-financial interests to disclose.

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Human blood samples were obtained under the auspices of the Medical Ethics Committee of Zhongnan Hospital of Wuhan University-approved protocol.

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Informed consent was obtained from all individual participants included in the study.

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Zou, M., Hu, X., Song, W. et al. Plasma LTBP2 as a potential biomarker in differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis: a pilot study. Clin Exp Med 23, 4809–4816 (2023). https://doi.org/10.1007/s10238-023-01214-x

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