Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis
Abstract Background Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-024-02809-y |
| _version_ | 1797199250628542464 |
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| author | Raisa Kraaijvanger Montse Janssen Bonás Jan C. Grutters Ioanna Paspali Marcel Veltkamp Dominique P. V. de Kleijn Coline H. M. van Moorsel |
| author_facet | Raisa Kraaijvanger Montse Janssen Bonás Jan C. Grutters Ioanna Paspali Marcel Veltkamp Dominique P. V. de Kleijn Coline H. M. van Moorsel |
| author_sort | Raisa Kraaijvanger |
| collection | DOAJ |
| description | Abstract Background Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. Objective In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. Methods Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). Results Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). Conclusion This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis. |
| first_indexed | 2024-04-24T07:12:46Z |
| format | Article |
| id | doaj.art-3fa121e54f9e4498b2f8d377a802a446 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-24T07:12:46Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-3fa121e54f9e4498b2f8d377a802a4462024-04-21T11:27:54ZengBMCRespiratory Research1465-993X2024-04-0125111210.1186/s12931-024-02809-yDecreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosisRaisa Kraaijvanger0Montse Janssen Bonás1Jan C. Grutters2Ioanna Paspali3Marcel Veltkamp4Dominique P. V. de Kleijn5Coline H. M. van Moorsel6Department of Pulmonology, St Antonius Hospital, Interstitial Lung Diseases Center of ExcellenceDepartment of Pulmonology, St Antonius Hospital, Interstitial Lung Diseases Center of ExcellenceDepartment of Pulmonology, St Antonius Hospital, Interstitial Lung Diseases Center of ExcellenceDepartment of Vascular Surgery, University Medical CenterDepartment of Pulmonology, St Antonius Hospital, Interstitial Lung Diseases Center of ExcellenceDepartment of Vascular Surgery, University Medical CenterDepartment of Pulmonology, St Antonius Hospital, Interstitial Lung Diseases Center of ExcellenceAbstract Background Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. Objective In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. Methods Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). Results Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). Conclusion This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.https://doi.org/10.1186/s12931-024-02809-yExtracellular vesiclesSarcoidosisBiomarkersTherapy |
| spellingShingle | Raisa Kraaijvanger Montse Janssen Bonás Jan C. Grutters Ioanna Paspali Marcel Veltkamp Dominique P. V. de Kleijn Coline H. M. van Moorsel Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis Respiratory Research Extracellular vesicles Sarcoidosis Biomarkers Therapy |
| title | Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| title_full | Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| title_fullStr | Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| title_full_unstemmed | Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| title_short | Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| title_sort | decreased serpin c1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis |
| topic | Extracellular vesicles Sarcoidosis Biomarkers Therapy |
| url | https://doi.org/10.1186/s12931-024-02809-y |
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