In addition, considering the cross-sectional nature of our data, we acknowledge that further prospective studies on large cohorts of SSc patients are required to ascertain whether, over time, changes in serum sNRP1 and Sema3E may correlate with the progression of NVC abnormalities and the development of certain complications such as DUs and gangrene, and whether sNRP1 and Sema3E levels at diagnosis may be predictive of a more severe peripheral vascular disease course, possibly helping in the choice of treatment. This evidence concerns the gene SEMA3E and gangrene.