The following is a summary of “Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis,” published in the April 2024 issue of Pulmonology by Kraaijvanger et al.
Sarcoidosis is a systemic granulomatous disease of unknown etiology that predominantly affects the lungs. Treatment becomes necessary when symptoms worsen, and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are commonly used anti-inflammatory therapies. However, there is significant variability in patient response to treatment, and reliable predictive markers are currently lacking.
This study aimed to investigate the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis collected before the initiation of therapy.
The study measured protein concentrations of a four-protein test panel of inflammatory proteins in EVs from a discovery cohort (n = 16) and a replication cohort (n = 129) of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of more than 5% in forced vital capacity (FVC) and/or more than 10% in the diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline.
The study found that serum protein levels varied between EV fractions and serum and between patients with sarcoidosis and healthy controls. Notably, Serpin C1 concentrations in the low-density lipid particle EV fraction were lower at baseline in patients who responded well to MTX treatment. This was observed in the discovery cohort (p = 0.059) and the replication cohort (p = 0.032). Furthermore, EV Serpin C1 emerged as a significant predictor for response to MTX treatment (OR 0.4; p = 0.032).
The findings of this study indicate that proteins isolated from EVs provide a distinct signal and hold potential as novel predictive biomarkers for therapy response in sarcoidosis. Specifically, lower baseline levels of Serpin C1 in EVs are associated with a favorable response to MTX treatment in patients with pulmonary sarcoidosis, suggesting that EV-derived biomarkers could guide personalized treatment strategies and improve clinical outcomes.
Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02809-y