A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia
Abstract Background Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during ac...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-018-0779-y |
| _version_ | 1811282552236802048 |
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| author | Jannie M. B. Sand Yoshinori Tanino Morten A. Karsdal Takefumi Nikaido Kenichi Misa Yuki Sato Ryuichi Togawa Xintao Wang Diana J. Leeming Mitsuru Munakata |
| author_facet | Jannie M. B. Sand Yoshinori Tanino Morten A. Karsdal Takefumi Nikaido Kenichi Misa Yuki Sato Ryuichi Togawa Xintao Wang Diana J. Leeming Mitsuru Munakata |
| author_sort | Jannie M. B. Sand |
| collection | DOAJ |
| description | Abstract Background Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers. Methods Patients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies. Results Sixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43–0.94], p = 0.022). Conclusions The ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations. |
| first_indexed | 2024-04-13T01:54:39Z |
| format | Article |
| id | doaj.art-0c8c62ba272449a78a8d8067784b39f0 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-13T01:54:39Z |
| publishDate | 2018-05-01 |
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| series | Respiratory Research |
| spelling | doaj.art-0c8c62ba272449a78a8d8067784b39f02022-12-22T03:07:47ZengBMCRespiratory Research1465-993X2018-05-011911910.1186/s12931-018-0779-yA Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial PneumoniaJannie M. B. Sand0Yoshinori Tanino1Morten A. Karsdal2Takefumi Nikaido3Kenichi Misa4Yuki Sato5Ryuichi Togawa6Xintao Wang7Diana J. Leeming8Mitsuru Munakata9Nordic Bioscience, Biomarkers and ResearchDepartment of Pulmonary Medicine, Fukushima Medical UniversityNordic Bioscience, Biomarkers and ResearchDepartment of Pulmonary Medicine, Fukushima Medical UniversityDepartment of Pulmonary Medicine, Fukushima Medical UniversityDepartment of Pulmonary Medicine, Fukushima Medical UniversityDepartment of Pulmonary Medicine, Fukushima Medical UniversityDepartment of Pulmonary Medicine, Fukushima Medical UniversityNordic Bioscience, Biomarkers and ResearchDepartment of Pulmonary Medicine, Fukushima Medical UniversityAbstract Background Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers. Methods Patients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies. Results Sixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43–0.94], p = 0.022). Conclusions The ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.http://link.springer.com/article/10.1186/s12931-018-0779-yVersicanExtracellular matrixBiomarkersIdiopathic interstitial pneumoniaAcute exacerbation |
| spellingShingle | Jannie M. B. Sand Yoshinori Tanino Morten A. Karsdal Takefumi Nikaido Kenichi Misa Yuki Sato Ryuichi Togawa Xintao Wang Diana J. Leeming Mitsuru Munakata A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia Respiratory Research Versican Extracellular matrix Biomarkers Idiopathic interstitial pneumonia Acute exacerbation |
| title | A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia |
| title_full | A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia |
| title_fullStr | A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia |
| title_full_unstemmed | A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia |
| title_short | A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia |
| title_sort | serological biomarker of versican degradation is associated with mortality following acute exacerbations of idiopathic interstitial pneumonia |
| topic | Versican Extracellular matrix Biomarkers Idiopathic interstitial pneumonia Acute exacerbation |
| url | http://link.springer.com/article/10.1186/s12931-018-0779-y |
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