Antithrombin glycoforms are selectively physiosorbed on plasma extracellular vesicles

Antithrombin (AT) is a glycoprotein produced by the liver and a principal antagonist of clotting factors. A deficit in AT function leads to AT qualitative deficiency, challenging to diagnose. Here we report that AT may travel physiosorbed on the surface of plasma extracellular vesicles (EVs), contributing to form the EV-protein corona. The corona is enriched in specific AT glycoforms, thus suggesting glycosylation to play a key role in AT partitioning between EVs and plasma. This is confirmed by the differences in AT glycoform composition of the corona of EVs separated from plasma of healthy and AT qualitative deficiency-affected subjects. This also supports the hypothesis of the role of altered glycosylation in AT deficiency, with promising translational diagnostic implications.