Abstract
BackgroundThe chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-β/Smad and VEGF-A may play a key role.MethodsWe evaluated immunoexpression of TGF-β1, Smad2, 3, and 7, and VEGF-A in serum and bronchoalveolar lavage (BAL) fluid of patients (n = 57) classified according to the presence of lung parenchymal involvement (radiological stage I vs. II-III), acute vs. insidious onset, lung function test (LFT) results, calcium metabolism parameters, percentage of BAL lymphocytes (BAL-L%), BAL CD4+/CD8+ ratio, age, and gender. Immunoexpression analysis of proteins was performed by ELISA.ResultsThe immunoexpression of all studied proteins were higher in serum than in BAL fluid of patients (p >0.05). The serum levels of TGF-β1 (p = 0.03), Smad2 (p = 0.01), and VEGF-A (p = 0.0002) were significantly higher in sarcoidosis patients compared to healthy controls. There were no differences within the sarcoidosis group between patients with vs. without parenchymal involvement, acute vs. insidious onset, or patients with normal vs. abnormal spirometry results. In patients with abnormal spirometry results a negative correlation was found between forced vital capacity (FVC) % predicted value and TGF-β1 immunoexpression in BAL fluid, and positive correlations were observed between the intensity of lung parenchymal changes estimated by high-resolution computed tomography (HRCT scores) and Smad 2 level in serum.ConclusionsTGF-β/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis. BAL TGF-β1, and Smad 2 in serum seem to be promising biomarkers with negative prognostic value, but further studies are required to confirmed our observations.
Highlights
The chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-β/Smad and Vascular Endothelial Growth Factor A (VEGF-A) may play a key role
The correlations between immunoexpression of the study proteins and selected biochemical and immunological markers and lung function parameters in serum and bronchoalveolar lavage (BAL) fluid We found few correlations between lung function parameters, selected laboratory markers, and protein levels in serum and BAL fluid of patients with pulmonary sarcoidosis (Table 3)
Statistically significantly differences in immunoexpression levels of selected proteins in serum and BAL fluid were not found between patients with abnormal compared to normal spirometry or between patients with restrictive or obstructive spirometric pattern and normal spirometry (P > 0.05, U Mann–Whitney test)
Summary
The chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-β/Smad and VEGF-A may play a key role. The diagnosis is made based on a clinical and radiological picture, and is usually confirmed by the presence of non-caseating granulomas in involved organs. The prognosis is relatively good; in about 60 % of patients with a plethora of phenotypes the disease disappears without any clinically significant remains. The most severe complication is lung fibrosis, occurring in 10–15 % of patients and leading to severe functional impairment, disability, and sometimes to death. Among different negative prognostic factors—lung interstitial disease, lung function test abnormality (of both restrictive and obstructive patterns), and severe impairment of calcium homeostasis may be listed as examples, whereas acute
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
