Serum Semaphorin 3a Levels in Patients With Behçet’s Disease With and Without Vascular Involvement

Abstract

Aim: Semaphorin 3A is a molecule with identified effects on vasculopathy, angiogenesis, the nervous system, bone homeostasis, and autoimmunity. Its role has been demonstrated in autoimmune and autoinflammatory diseases. In the pathogenesis of Behçet’s disease, autoinflammation and vasculopathy play significant roles. While some Behçet’s disease patients present with vasculopathy, no biomarker has yet been identified to predict which patients will develop vasculopathy. Our study aims to determine serum semaphorin 3A levels in Behçet's disease patients and establish its potential role as a biomarker for diagnosis, disease activity, and vasculopathy. Methods: Our study included 97 Behçet’s disease patients who were followed up in the last 6 months at the Ankara City Hospital Rheumatology Clinic and 48 healthy volunteers who accepted to be included in the study. The patient group was initially divided into two categories: vascular and non-vascular. The vascular group included 46 patients with deep vein thrombosis, thrombophlebitis, or pulmonary arterial aneurysm, while the non-vascular group consisted of 51 Behçet’s disease patients without any thromboembolic events or other vascular involvement associated with Behçet's disease.The control group included 48 healthy volunteers without any systemic diseases, malignancies, autoimmune or autoinflammatory diseases, or a history of active or past thromboembolic disease, and who did not smoke or use any medication. The serum semaphorin 3A levels of the patients and healthy volunteers participating in the study were measured using the ELISA method and were statistically evaluated through comparative analysis. Results: The mean age of Behçet’s patients and the control group was similar 42.95 ± 10.96 vs. 40.64 ± 10.06 years. The average serum semaphorin 3A level of all Behçet’s patients was found to be 46.76 (11.15) ng/mL, while the average semaphorin 3A level in the control group was determined to be 60 (23.79) ng/mL. The serum semaphorin 3A level of Behçet’s patients was found to be statistically significantly lower compared to the control group (p < 0.001). The average serum semaphorin 3A level in the vascular group was determined to be 43.96 (7.52) ng/mL, whereas the serum semaphorin 3A level in non-vascular Behçet’s patients was 49.28 (13.20) ng/mL. The serum semaphorin 3A level of vascular Behçet’s patients was found to be statistically significantly lower compared to non-vascular Behçet’s patients (p = 0.016). The semaphorin 3A levels of both groups were found to be statistically significantly lower compared to the control group (vascular/control p < 0.001; non-vascular/control p = 0.006). Conclusions: Serum semaphorin 3A levels were significantly decreased in both vascular and non-vascular Behçet's groups compared to controls. This is the first study in Behçet's patients to suggest semaphorin 3A as a potential biomarker of inflammation and vascular involvement. © The Author(s), under exclusive licence to the Faculty of Medicine, Comenius University in Bratislava 2025.