We demonstrated elevated levels of all investigated circulating EVs (EEVs, PEVs, LEVs, ICAM1 + EVs, TF + EVs, and HMGB1 + EVs) in patients with SSc-ILD compared to patients without SSc-ILD or controls, as well as an inverse correlation with the respiratory function tests at baseline. This evidence concerns the gene HMGB1 and interstitial lung disease.