Newly found 3-protein signature may help to diagnose IPF

Potential biomarker found to distinguish IPF from other lung diseases

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A three-protein signature can be used to differentiate between idiopathic pulmonary fibrosis (IPF) and other lung disorders and may be a noninvasive biomarker of the rare disease, according to a new study.

While the scientists stressed that further research will be needed to validate the clinical utility of this protein signature, they suggest that it could be used to help in diagnosing IPF.

“The diagnostic work up of IPF and other [lung diseases] is still evolving and there is risk of misdiagnosis. To the best of our knowledge, this is the first … noninvasive protein signature [of its kind] for IPF diagnosis,” the researchers wrote.

The study, “Plasma extracellular vesicle proteins as promising noninvasive biomarkers for diagnosis of idiopathic pulmonary fibrosis,” was published in the Journal of Extracellular Biology.

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New protein signature shows promise as biomarker

Diagnosing IPF can be a challenge. While imaging tests can be useful for identifying IPF-like lung damage, other lung disorders also can cause similar patterns of lung damage, making it difficult for clinicians to distinguish between these different diseases.

Now, a team led by researchers in the U.S. tested whether measuring proteins inside of extracellular vesicles (EVs) could be used to help identify IPF. EVs are basically small packets of cellular materials, which are released by many different types of cells as part of cell-to-cell communication processes.

“We aimed to identify a protein signature in EVs that distinguishes IPF from other [interstitial lung diseases] and healthy [people],” the scientists wrote.

The team evaluated the contents of EVs from the blood of 20 people with IPF and 19 people with other lung diseases — specifically chronic hypersensitivity pneumonitis (CHP) and nonspecific interstitial pneumonitis (NSIP). The contents of EVs from 20 individuals without any lung disease, who served as healthy controls, also were examined.

From the analysis, researchers identified five proteins that were present at significantly altered levels in IPF patients. These were high mobility group box protein 1 (HMGB1), surfactant protein B (SFTPB), Aldolase A (ALDOA), calmodulin like 5 (CALML5), and Talin-1 (TLN1).

Further tests showed that using just three of these proteins — HMGB1, CALML5, and TLN1 — allowed the differentiation between IPF patients and those with other lung diseases.

These results suggest that our EV protein biomarker panel has good efficacy in differential diagnosis of IPF.

To test the utility of this three-protein signature, the researchers calculated a statistical measure called the area under the receiver operating characteristic curve, or AUROC. This measure basically reflects how well a given test can distinguish between two groups. In this case, the groups were patients with IPF and those without the chronic lung disease. Higher AUROC values indicate a better discrimination between the two groups being analyzed.

In an independent set of EVs from 10 people with IPF and 23 with other lung diseases, the three-protein signature showed an AUROC of 0.866 for distinguishing IPF.

“These results suggest that our EV protein biomarker panel has good efficacy in differential diagnosis of IPF,” the researchers concluded, though they noted that “these markers need to be validated in large-scale prospective cohort studies to establish their usability in clinics.”

Further analyses showed that just two EV proteins, CALML5 and HMGB1, could be used to distinguish between people with IPF and those without lung disease. In an independent group of 10 people with IPF and 12 patients without lung disease (healthy individuals), the AUROC was 0.924.

According to the researchers, the findings “suggest that the EV biomarkers have excellent efficacy in discriminating IPF from healthy [people],” the researchers wrote, again stressing a need for further research to validate these findings.

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