Considering the complex pathogenesis of SSc-ILD, we decided to perform a pilot study exploring the levels of circulating EEVs, PEVs, and LEVs, along with EVs exposing TF, ICAM1, or HMGB1 in patients with SSC-ILD, as well as a cohort that investigates the onset of ILD progression over a 3-year follow-up period. Here, HMGB1 is linked to interstitial lung disease.