Serum Endoglin as a Predictive Biomarker for Active Digital Ulcers in Systemic Sclerosis: A Case-Control Study

Introduction This study aimed to evaluate soluble endoglin (sENG) in serum as a potential biomarker of active digital ulcers (DUs) in systemic sclerosis (SSc). Methods This single-center, cross-sectional case-control study included 60 SSc patients, comprising 30 with active DUs and 30 without active DUs, and 30 age- and sex-matched healthy controls. Serum sENG levels were measured using enzyme-linked immunosorbent assay. Results Median sENG levels were highest in SSc patients with active DUs, followed by those without active DUs and healthy controls: 0.54, 0.28, and 0.19 ng/mL, respectively. Patients with active DUs had significantly higher sENG levels than those without active DUs ( p = 0.0007). Among SSc patients without active DUs, sENG levels did not differ significantly between those with previous but inactive DUs and those who had never had DUs ( p = 0.344). In contrast, patients with active DUs had significantly higher sENG levels than both DU-naïve patients ( p = 0.009) and patients with previous but inactive DUs ( p < 0.05). ROC analysis showed that an sENG cut-off of 0.24 ng/mL differentiated SSc patients from healthy controls, with an AUC of 0.91, while a cut-off of 0.43 ng/mL discriminated SSc patients with active DUs from those without active DUs, with an AUC of 0.75. sENG levels were positively correlated with the number of active DUs (rho = 0.39, p = 0.002), but not with DUCAS-assessed DU severity (rho = -0.09, p = 0.65). Higher sENG levels were also associated with active/late nailfold capillaroscopy patterns and elevated systolic pulmonary arterial pressure. Discussion These findings suggest that serum sENG may reflect active DU-related microvascular injury rather than remote DU history alone. Its association with active ulcer burden, advanced nailfold capillaroscopy patterns, and elevated systolic pulmonary arterial pressure supports its potential role as an accessible adjunctive biomarker of active vascular involvement in SSc, although longitudinal validation is required. Conclusion Serum sENG may serve as a potential biomarker of active DU burden and ongoing microvascular injury in SSc.