C-proSP-B: A Possible Biomarker for Pulmonary Diseases?

Kahn, Nicolas; Rossler, Anne-Kathrin; Hornemann, Katrin; Muley, Thomas; Grünig, Ekkehard; Schmidt, Werner; Herth, Felix J.F.; Kreuter, Michael

doi:10.1159/000488245

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…A number of peripheral blood biomarkers have been studied that can aid in delineating ILDs from other severe lung diseases. The markers Krebs von den Lungen (KL)-6 [24], chitinase-like protein (YKL40) [41,56], leucocytes and circulating innate immune cells [57][58][59], surfactant proteins (SP)-A, -B, -D, among others, have been shown to discriminate IPF from healthy controls [25,27,31]. KL-6 may also discriminate ILDs from other benign lung diseases [24,60].…”

Section: Diagnostic Biomarkersmentioning

confidence: 99%

The therapy of idiopathic pulmonary fibrosis: what is next?

et al. 2019

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I–III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

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Section: Diagnostic Biomarkersmentioning

confidence: 99%

The therapy of idiopathic pulmonary fibrosis: what is next?

et al. 2019

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“…Our protein signature comprised of SFTPB, ALDOA, HMGB1, CALML5 and TLN1. SFTPB levels in serum of IPF patients are known to be elevated 32 and are associated with poor survival 33 .…”

Section: Discussionmentioning

confidence: 99%

“…Our protein signature comprised of SFTPB, ALDOA, HMGB1, CALML5 and TLN1. SFTPB levels in serum of IPF patients are known to be elevated 32 and are associated with poor survival 33 . Similarly, proteomic analysis of broncho-alveolar lavage fluid (BALF) revealed upregulation of ALDOA in IPF patients presented with acute exacerbations 34 .…”

Section: Discussionmentioning

confidence: 99%

A novel protein signature from plasma extracellular vesicles for non-invasive differential diagnosis of idiopathic pulmonary fibrosis

Adduri

Cai

et al. 2021

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Background: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia of unknown etiology often leading to respiratory failure. Over half of IPF patients present with discordant features of usual interstitial pneumonia on high-resolution computed tomography at diagnosis which warrants surgical lung biopsy to exclude the possibility of other interstitial lung diseases (ILDs). Therefore, there is a need for non-invasive biomarkers for expediting the differential diagnosis of IPF. Methods: Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in a cohort of subjects with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects (HS). A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. We evaluated the concordance between plasma EV proteome and the lung transcriptome data. Lastly, we compared the molecular pathways overrepresented in IPF by differentially expressed proteins and transcripts from EVs and lung tissues, respectively. Results: The five-protein signature derived from mass spectrometry data showed area under the receiver operating characteristic curve of 0.915 (95%CI: 0.819-1.011) and 0.958 (95%CI: 0.882-1.034) for differentiating IPF from other ILDs and from HS, respectively. We also found that the EV protein expression profiles mirrored their corresponding mRNA expressions in IPF lungs. Further, we observed an overlap in the EV proteome- and lung mRNA-associated molecular pathways. Conclusions: We discovered a plasma EV-based protein signature for differential diagnosis of IPF and validated this signature in an independent cohort. The signature needs to be tested in large prospective cohorts to establish its clinical utility.

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“…Several serum biomarkers of IPF severity and progression have been studied and characterized [32]. These include matrix metalloproteinases 1 and 7 [33], surfactant proteins SP-A and SP-D [34], SP-B [35] and fibulin-1 [36]. However, there is not a single biomarker that can accurately diagnose and predict likelihood of progression of IPF.…”

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin is elevated in pulmonary fibrosis and associates with IPF progression

Habibie

Putri

Boorsma

et al. 2020

Preprint

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Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-kB ligand (RANKL), is used as a biomarker for assessing severity of liver fibrosis. However, its expression and role in pulmonary fibrosis are unknown. We hypothesized that OPG also has a role in pulmonary fibrosis.Human and mouse control and fibrotic lung tissue were used to examine OPG expression, and mouse precision-cut lung slices to study OPG regulation in pulmonary fibrosis. Serum from idiopathic pulmonary fibrosis (IPF) patients and controls was analysed to investigate whether OPG levels correlate with disease status as measured by lung function.OPG-protein levels were significantly higher in mouse and human fibrotic lung tissue compared to control. OPG-mRNA and protein production were induced in mouse precision-cut-lung slices upon TGFβ stimulation and could be inhibited with galunisertib, a TGFβ receptor kinase inhibitor. OPG-protein levels in fibrotic mouse lung tissue correlated with degree of fibrosis. Isolated lung fibroblasts from IPF patients had higher OPG-protein levels than control fibroblasts. Serum OPG levels in IPF patients, at first presentation, negatively correlated with diffusing capacity to carbon monoxide. Finally, serum OPG levels higher than 1234 pg/ml at first presentation were associated with progression of disease in IPF patients.In conclusion, OPG is produced in lung tissue, associates with fibrosis, and may be a potential prognostic biomarker for IPF disease progression. Validation in a larger cohort is warranted to further explore the role of OPG in pulmonary fibrosis and its potential for assessing the prognosis of fibrotic lung disease in individual patients.Take home messageOsteoprotegerin is present in fibrotic lung tissue and high serum levels correlate with low lung function and IPF disease progression in this small study, indicating osteoprotegerin may have value as a biomarker to predict IPF progression

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C-proSP-B: A Possible Biomarker for Pulmonary Diseases?

Cited by 16 publications

References 27 publications

The therapy of idiopathic pulmonary fibrosis: what is next?

The therapy of idiopathic pulmonary fibrosis: what is next?

A novel protein signature from plasma extracellular vesicles for non-invasive differential diagnosis of idiopathic pulmonary fibrosis

Osteoprotegerin is elevated in pulmonary fibrosis and associates with IPF progression

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