A systematic review and meta-analysis of the endothelial-immune candidate biomarker endoglin in rheumatic diseases

Existing challenges in accurately diagnosing various rheumatic diseases (RDs) have stimulated the search for novel biomarkers to aid clinical evaluation and monitoring. We conducted a systematic review and meta-analysis of studies investigating the candidate biomarker endoglin (CD105), a transmembrane glycoprotein expressed in endothelial, myeloid, and lymphoid cells, in RD patients and healthy controls. We searched PubMed, Scopus, and Web of Science from inception to 10 August 2024 to identify relevant studies. We evaluated the risk of bias using the JBI Critical Appraisal Checklist and the certainty of evidence using GRADE (PROSPERO registration number: CRD42023581008). Overall, circulating endoglin concentrations were significantly higher in RD patients compared to controls (13 studies; standard mean difference, SMD = 0.64, 95% CI 0.13 to 1.14, p = 0.014; low certainty of evidence). The effect size of the between-group differences in endoglin concentrations was not significantly associated with age, male-to-female ratio, year of publication, number of participants, or mean RD duration. By contrast, the effect size was statistically significant in studies conducted in the European region (p = 0.033), involving patients with systemic sclerosis (p = 0.032), and measuring serum (p = 0.019). The results of this systematic review and meta-analysis suggest the potential pathophysiological role of endoglin in RDs. This, however, requires further investigation in prospective studies, particularly in patients with systemic sclerosis.