Gas6/TAM system as potential biomarker for multiple sclerosis prognosis

Gas6/TAM 系统作为多发性硬化症预后的潜在生物标志物

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作者:Davide D'Onghia #, Donato Colangelo #, Mattia Bellan, Stelvio Tonello, Chiara Puricelli, Eleonora Virgilio, Daria Apostolo, Rosalba Minisini, Luciana L Ferreira, Leonardo Sozzi, Federica Vincenzi, Roberto Cantello, Cristoforo Comi, Mario Pirisi, Domizia Vecchio, Pier Paolo Sainaghi

Conclusions

Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Methods

In a prospective cohort study, we enrolled 64 patients with a diagnosis of clinical isolated syndrome (CIS), radiological isolated syndrome (RIS) and relapsing-remitting (RR) MS according to the McDonald 2017 Criteria. Before any treatment initiation, we sampled the serum and CSF, and collected clinical data: disease course, presence of gadolinium-enhancing lesions, and expanded disability status score (EDSS). At the last clinical follow-up, we assessed EDSS and calculated MS severity score (MSSS) and age-related MS severity (ARMSS). Gas6 and TAM receptors were determined using an ELISA kit (R&D Systems) and compared to neurofilament (NFLs) levels evaluated with SimplePlex™ fluorescence-based immunoassay.

Results

At diagnosis, serum sAxl was higher in patients receiving none or low-efficacy disease-modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Higher CSF Gas6 and serum sAXL were associated with an EDSS <3 at diagnosis (p = 0.04; p = 0.037). Serum Gas6 correlates to a lower MSSS (r2 = -0.32, p = 0.01). Serum and CSF NFLs were confirmed as disability biomarkers in our cohort according to EDSS (p = 0.005; p = 0.002) and MSSS (r2 = 0.27, p = 0.03; r2 = 0.39, p = 0.001). Results were corroborated using multivariate analysis. Conclusions: Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

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