SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis

Progressive pulmonary fibrosis (PPF) is a serious condition that involves the worsening of various interstitial lung diseases (ILDs). One of the major challenges in managing PPF is the lack of effective biomarkers that can help identify patients at risk early on. Recent research, however, is shedding light on promising new biomarkers that could transform how we detect and treat this debilitating condition.

What is Progressive Pulmonary Fibrosis?

PPF refers to the progressive scarring and thickening of the lung tissues, which leads to a decline in lung function over time. This condition can arise from various types of ILDs, making it a significant health concern. The main issue with PPF is that by the time it’s diagnosed, the disease has often advanced, limiting treatment options.

The Search for Better Biomarkers

Biomarkers are biological indicators that can be measured to assess the presence or progression of a disease. Current biomarkers for ILDs include serum KL-6 and SP-D, but these markers are not always reliable in predicting the progression of PPF. To address this, researchers have been investigating new ways to identify at-risk patients earlier.

Proteomic Analysis of Serum Extracellular Vesicles

A breakthrough came from a study that performed a proteomic analysis of serum extracellular vesicles (EVs). EVs are tiny particles secreted by cells that carry proteins and other molecules, playing a crucial role in cell communication. By analyzing the proteins within these EVs, researchers at Osaka University hoped to find new biomarkers specifically linked to lung fibrosis.

Discovery of SFTPB as a Key Biomarker

Among the proteins identified, pulmonary surfactant-associated protein B (SFTPB) stood out. SFTPB is involved in maintaining the surface tension in the lungs, which is essential for proper lung function. The study found that levels of SFTPB in serum EVs could predict ILD progression more accurately than the existing biomarkers, KL-6 and SP-D. Notably, SFTPB was identified as an independent prognostic factor, meaning it could provide valuable information about disease progression regardless of other factors like gender, age, and lung function.

Evaluating SFTPB in Different Cohorts

To validate these findings, the utility of SFTPB was tested in two different patient cohorts. The results were promising: SFTPB in serum EVs, but not in the serum itself, was effective in predicting the progression of ILDs. This distinction is crucial because it highlights the importance of analyzing EVs rather than just the serum.

The Role of Pro-SFTPB

Further analysis revealed that a specific form of SFTPB, known as pro-SFTPB, was particularly elevated in patients with PPF. This was consistent in both human patients and a mouse model of lung fibrosis. Pro-SFTPB primarily originates from alveolar epithelial type 2 cells in the lungs, and its increased levels in serum EVs mirrored the fibrotic changes occurring in the lungs.

Implications for Clinical Practice

The identification of SFTPB, especially its pro-form in serum EVs, as a biomarker for PPF is a significant advancement. It means that we might soon have a reliable tool to detect the progression of ILDs earlier and more accurately. This could lead to earlier interventions, potentially slowing the progression of the disease and improving patient outcomes.


The discovery of SFTPB as a biomarker for progressive pulmonary fibrosis marks a significant step forward in the fight against ILDs. By focusing on serum EVs, these researchers have uncovered a more precise method for predicting disease progression. As this research continues to develop, it holds the promise of better diagnostic tools and more effective treatments for patients suffering from this challenging condition.

Enomoto T, Shirai Y, Takeda Y, Edahiro R, Shichino S, Nakayama M, Takahashi-Itoh M, Noda Y, Adachi Y, Kawasaki T, Koba T, Futami Y, Yaga M, Hosono Y, Yoshimura H, Amiya S, Hara R, Yamamoto M, Nakatsubo D, Suga Y, Naito M, Masuhiro K, Hirata H, Iwahori K, Nagatomo I, Miyake K, Koyama S, Fukushima K, Shiroyama T, Naito Y, Futami S, Natsume-Kitatani Y, Nojima S, Yanagawa M, Shintani Y, Nogami-Itoh M, Mizuguchi K, Adachi J, Tomonaga T, Inoue Y, Kumanogoh A. (2024) SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis. JCI Insight 9(11):e177937. [article]

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